The methods and strategies used to screen for syphilis and to confirm initially reactive results can vary significantly across clinical laboratories.While the performance characteristics of these different approaches ...The methods and strategies used to screen for syphilis and to confirm initially reactive results can vary significantly across clinical laboratories.While the performance characteristics of these different approaches have been evaluated by multiple studies,there is not,as of yet,a single,universally recommende dalgorithm for syphilis testing.To clarify the currently available options for syphilis testing,this update will summarize the clinical challenges to diagnosis,review the specific performance characteristics of treponemal and non-treponemal tests,and finally,summarize select studies published over the past decade which have evaluated these approaches.Specifically,this review will discuss the traditional and reverse sequence syphilis screening algorithms commonly used in the United States,alongside a discussion of the European Centre for Disease Prevention and Control syphilis algorithm.Ultimately,in the United States,the decision of which algorithm to use is largely dependent on laboratory resources,the local incidence of syphilis and patient demographics.展开更多
The average age of hepatitis C virus(HCV)-infected individuals is becoming increasingly higher in Japan and steps should be taken to treat older individuals infected with HCV. Until an interferon-free regimen becomes ...The average age of hepatitis C virus(HCV)-infected individuals is becoming increasingly higher in Japan and steps should be taken to treat older individuals infected with HCV. Until an interferon-free regimen becomes available, peginterferon plus ribavirin will play a critical role in the treatment. The perception that older HCVinfected patients may be at higher risk than younger patients for adverse events from peginterferon plus ribavirin treatment but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials. A recent genomewide association study revealed that interleukin-28B(IL28B) genotype closely correlates with the treatment response against HCV. The relationship of IL28 B genotype with the treatment response in older HCV-infected patients is also unknown. In this review, we focused on the treatment response in older patients infected with HCV and the effects of IL28 B genotype. IL28 B major genotype is a useful predictor of sustained virological response in the interferon-including treatment of older patients infected with HCV. It also seems useful for avoiding adverse events, although the mechanisms ofthe effects of IL28 B genotype on the treatment outcome are still poorly understood and are currently under investigation. Further studies will be needed.展开更多
Sj?gren's syndrome(SS) is a systemic autoimmune disease that affects primarily the lacrimal and salivary glands. In addition to a systemic autoimmune response directed against ubiquitous antigens(such as Ro and La...Sj?gren's syndrome(SS) is a systemic autoimmune disease that affects primarily the lacrimal and salivary glands. In addition to a systemic autoimmune response directed against ubiquitous antigens(such as Ro and La antigens),patients with SS mount a localized response that affects the epithelial component of exocrine glands leading to the establishment of a destructive inflammatory infiltrate comprised of activated T and B cells. Local chemokine and cytokine production drive the recruitment and local activation of immune cells that cause injury to acinar cells. CD4 T cells with different functional differentiation programs including Th1(IFN-γ),Th2(IL-13,IL-4) and Th17(IL-17,IL-21,IL-22) as well as diverse cytokine signaling pathways,are involved at the initiation,perpetuation,and progression of the disease. Which factors initiate this response and allow it to become chronic are unknown. Proposed mechanisms include viral infections and acinar cell apoptosis. Moreover risk-conferring genetic variants,probably through the facilitation of innate and adaptive immune activation,most certainly contribute to the creation of an underlying environment that fosters tolerance loss and facilitates perpetuation of the autoimmune response. In this review,we describe the mechanisms through which the immune response causes SS and emphasize the pathways that are amenable of being targeted with therapeutic purposes.展开更多
Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include p...Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include programmed death-1(PD-1), cytotoxic T lymphocyte associated antigen-4(CTLA-4), lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, Glucocorticoid-induced TNFR family-related receptor(GITR), and killer cell immunoglobulin like receptor. With the exception of GITR, after binding to their respective ligands these checkpoints induce down-modulation of immune responses to prevent autoimmunity. However, such immune mechanisms are co-opted by tumors to allow rapid tumor cell proliferation. Pre-clinical studies in antibody blockade of PD-1 and CTLA-4 have led to promising augmentation of effector immune responses in murine tumor models, and human antibodies against PD-1 and CTLA-4 alone or in combination have demonstrated tumor regression in clinical trials. The development of immune checkpoint blockade as a potential future immunotherapy has led to increasing interest in combining treatment modalities. Combination checkpoint blockade with chemotherapy and radiation therapy has shown synergistic effects in pre-clinical and clinical studies, and combination checkpoint blockade with bacterial vaccine vectors have produced increased effector immune responses in pre-clinical models. The future of immune checkpoint blockade may be as a powerful adjuvant alongside the current standard of care.展开更多
Viral protein U(Vpu) is an accessory protein associated with two main functions important in human immunodeficiency virus type 1(HIV-1) replication and dissemination; these are down-regulation of CD4 receptor through ...Viral protein U(Vpu) is an accessory protein associated with two main functions important in human immunodeficiency virus type 1(HIV-1) replication and dissemination; these are down-regulation of CD4 receptor through mediating its proteasomal degradation and enhancement of virion release by antagonizing tetherin/BST2. It is also well established that Vpu is one of the most highly variable proteins in the HIV-1 proteome. However it is still unclear what drives Vpu sequence variability, whether Vpu acquires polymorphisms as a means of immune escape, functional advantage, or otherwise. It is assumed that the host-pathogen interaction is a cause of polymorphic phenotype of Vpu and that the resulting functional heterogeneity of Vpu may have critical significance in vivo. In order to comprehensively understand Vpu variability, it is important to integrate at the population level the genetic associationapproaches to identify specific amino acid residues and the immune escape kinetics which may impose Vpu functional constraints in vivo. This review will focus on HIV-1 accessory protein Vpu in the context of its sequence variability at population level and also bring forward evidence on the role of the host immune responses in driving Vpu sequence variability; we will also highlight the recent findings that illustrate Vpu functional implication in HIV-1 pathogenesis.展开更多
Five major porcine coronaviruses(COVs)have been identified which cause severe gastrointestinal(GI)and respiratory disease in pigs.They include transmissible gastroenteritis(TGEV),porcine epidemic diarrhea virus(PEDV),...Five major porcine coronaviruses(COVs)have been identified which cause severe gastrointestinal(GI)and respiratory disease in pigs.They include transmissible gastroenteritis(TGEV),porcine epidemic diarrhea virus(PEDV),porcine deltacoronavirus,porcine respiratory coronavirus,and porcine hemagglutinating encephalomyelitis.These diseases,especially TGEV and PEDV,have caused epidemics in Europe,Asia,and the Americas over the past 50 years,causing significant economic losses to swine producers.As pigs are a major protein source worldwide there is great interest in understanding,controlling,and preventing these diseases.These diseases have no cure,and current vaccines are not fully protective.On-farm prevention and biosecurity are difficult to enforce and have not stopped the spread of these diseases between herds.Recent advances in the immunology of porcine COVs has revealed that the immune response to porcine COVs shares many similarities with the response to human COVs,leading to increased interest in pigs as models for human disease.Highlights of these advances include the key role of local antigen presenting cells in the gastrointestinal tract in stimulating a protective immune response.This understanding has lead to new proposed vaccines.Advances in the understanding of the ways the viruses evade and degrade the host immune system have also lead to novel proposed therapies.Many of these therapies are in the early development stages,as researchers attempt to create efficacious,cost-effective,and practical therapies for these diseases.展开更多
Free radicals(reactive oxygen species,superoxides and hydroxyl radicals)lead to the development of oxidative stress because of imbalance in the amount of antioxidants.Continued development of oxidative stress leads to...Free radicals(reactive oxygen species,superoxides and hydroxyl radicals)lead to the development of oxidative stress because of imbalance in the amount of antioxidants.Continued development of oxidative stress leads to chronic diseases in humans.The instability in the antioxidant activities and accumulation of oxidative stress due to free radicals may occur in diseases like inflammatory bowel disease(IBD).Antioxidants are substances that inhibit or delay the mechanism of oxidation of molecules mediated by free radicals and also transform into lesseractive derivatives.Probiotics are defined as live microorganisms that show beneficial effects on inflamed intestine and balance the inflammatory immune responses in the gut.Probiotic strains have been reported to scavenge hydroxyl radicals and superoxide anions that are abundantly produced during oxidative stress.The most widely studied probiotic strains are Streptococcus,Bifidobacterium and Lactobacillus.Probiotics cultured in broth have shown some amount of antioxidant activities.Fermented milk and soy milk,which possess starter microorganisms(probiotics),tends to increase the antioxidant activities manyfold.This review aims to discuss the in vivo and in vitro antioxidant activities of specific probiotics with various assays with respect to IBD.展开更多
There is a major transformation in gene expression between mature B cells(including follicular,marginal zone,and germinal center cells) and antibody secreting cells(ASCs),i.e.,ASCs,(including plasma blasts,splenic pla...There is a major transformation in gene expression between mature B cells(including follicular,marginal zone,and germinal center cells) and antibody secreting cells(ASCs),i.e.,ASCs,(including plasma blasts,splenic plasma cells,and long-lived bone marrow plasma cells). This significant change-over occurs to accommodate the massive amount of secretory-specific immunoglobulin that ASCs make and the export processes itself. It is well known that there is an up-regulation of a small number of ASC-specific transcription factors Prdm1(B-lymphocyte-induced maturation protein 1),interferon regulatory factor 4,and Xbp1,and the reciprocal downregulation of Pax5,Bcl6 and Bach2,which maintain the B cell program. Less well appreciated are the major alterations in transcription elongation and RNA processing occurring between B cells and ASCs. The three ELL family members ELL1,2 and 3 have different protein sequences and potentially distinct cellular roles in transcription elongation. ELL1 is involved in DNA repair and small RNAs while ELL3 was previously described as either testis or stem-cell specific. After B cell stimulation to ASCs,ELL3 levels fall precipitously while ELL1 falls off slightly. ELL2 is induced at least 10-fold in ASCs relative to B cells. All of these changes cause the RNA Polymerase Ⅱ in ASCs to acquire different properties,leading to differences in RNA processing and histone modifications.展开更多
An important percentage of colorectal cancer(CRC) patients will develop metastasis,mainly in the liver,even after a successful curative resection.This leads to a very high mortality rate if metastasis is not detected ...An important percentage of colorectal cancer(CRC) patients will develop metastasis,mainly in the liver,even after a successful curative resection.This leads to a very high mortality rate if metastasis is not detected early on.Disseminated cancer cells develop from metastatic stem cells(Met SCs).Recent knowledge has accumulated about these cells particularly in CRC,so they may now be tracked from the removed primary tumour.This approach could be especially important in prognosis of metastasis because it is becoming clear that metastasis does not particularly rely on testable driver mutations.Among the many traits supporting an epigenetic amplification of cell survival and self-renewal mechanisms of Met SCs,the role of many immune cell populations present in tumour tissues is becoming clear.The amount of tumour-infiltrating lymphocytes(T,B and natural killer cells),dendritic cells and some regulatory populations have already shown prognostic value or to be correlated with disease-free survival time,mainly in immunohistochemistry studies of unique cell populations.Parallel analyses of these immune cell populations together with Met SCs in the primary tumour of patients,with later follow-up data of the patients,will define the usefulness of specific combinations of both immune and Met SCs cell populations.It is expected that these combinations,together to different biomarkers in the form of an immune score,may predict future tumour recurrences,metastases and/or mortality in CRC.It will also support the future design of improved immunotherapeutic approaches against metastasis.展开更多
Pancreatic cancer has an overall 5-year survival rate of less than 5%.Unfortunately,patient survival has not substantially improved in the last couple of decades despite advances in treatment modalities that have been...Pancreatic cancer has an overall 5-year survival rate of less than 5%.Unfortunately,patient survival has not substantially improved in the last couple of decades despite advances in treatment modalities that have been successful in other cancer types.The poor response of pancreatic cancer to therapy is a majo obstacle faced by clinicians.Increasing attention is bein paid to how tumor cells and non-tumor cells influenc each other in the pancreatic tumor microenvironment Tumor-associated macrophages(TAMs)are a highligh in this field because of their vast presence in th tumor microenvironment.TAMs promote angiogenesis metastasis,and suppress the anti-tumor immun response.Here we review the current understandin of the role of TAMs in regulating the progression o pancreatic cancer.展开更多
Sézary syndrome(SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically display...Sézary syndrome(SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically displays a CD3+ CD4+ CD45RO+ memory T cell phenotype. We report a case of SS with an aberrant CD56+ immunophenotype. This patient presented with a generalized erythroderma and palpable small axillary lymph nodes.SS(stage IVA) was diagnosed on histological criteria and by the detection of a major T cell clone in skin and blood, an elevated CD4/CD8 T cell ratio and Sézary cells count > 1000/mm3. Beside the Sézary cell marker KIR3DL2, immunostainings revealed that two third of the malignant cells expressed CD56 but no other natural killer(NK) cell marker such as CD16, CD160 or NKp46. This atypical expression was not linked to an activation-dependent process and remained stable during the time course of the disease. No loss of the panT-cell markers CD2, CD3 or CD4 was detected while a complete down-modulation of CD26 was observed. Despite several lines of treatment, no durable amelioration was observed and patient died after 10 mo of follow-up. Because this CD4+ CD56+ SS case is the only one reported so far, the functional significance of CD56 expression remained difficult to assess in terms of aggressiveness and prognosis.展开更多
Ulcerative colitis and Crohn's disease, collectively termed the inflammatory bowel diseases(IBD), are chronic inflammatory disorders of the gastrointestinal tract. A "dysbiotic" relationship between the ...Ulcerative colitis and Crohn's disease, collectively termed the inflammatory bowel diseases(IBD), are chronic inflammatory disorders of the gastrointestinal tract. A "dysbiotic" relationship between the commensal gut flora and the intestinal mucosa-associated immune system has been at the core of the pathogenesis of these conditions. Probiotics are "good bacteria" with the ability to benefit the health of the host and their therapeutic application has been studied in IBD. The theoretical basis for such utilization relies upon the ability of probiotic microorganisms to interfere with the dysregulated homeostasis that takes place in IBD and restore the immune-bacterial interaction at the intestinal mucosa. Proposed mechanisms of action include the reconstitution of altered flora composition, enhancement of the integrity of the epithelial barrier, promotion of tolerogenic action by dendritic cells, strengthening of the defensive mechanisms of the innate immunity, and the suppression of pro-inflammatory adaptive immune responses. Despite this abundance of supporting experimental evidence, clinical application of probiotics in IBD has been disappointing. Possible explanations for such discrepancy include the great diversity of microorganisms that fall under the definition of probiotics, the lack of standardization of dosages and administration schemes, the heterogeneity between clinical trials, and the inclusion in the treatment arms of patients with a large variety of clinical phenotypes. Addressing these important issues will be critical for the optimal usage of probiotic-based therapies for patients with IBD.展开更多
Liver disease has recently been described as an important cause of morbidity and mortality in patients infected with human immunodeficiency virus(HIV). Liver test changes are useful surrogates of the burden of liver d...Liver disease has recently been described as an important cause of morbidity and mortality in patients infected with human immunodeficiency virus(HIV). Liver test changes are useful surrogates of the burden of liver disease. Previous studies have shown that transaminase elevations are frequent among these patients. The cause of those changes is harder to establish in HIV-patients. We present a 61-year-old caucasian male,diagnosed with HIV type 1 infection since 1998,under highly active antiretroviral treatment(HAART),with virological suppression and immunological recovery. He presented in a follow-up laboratory workup high values of transaminases,arthralgia at the hip joints and hepatomegaly. Liver function tests were normal. The antibodies to hepatitis viruses were negative. However,autoimmune study and liver biopsy were compatible with autoimmune hepatitis(AIH). The AIH is a rare di-agnosis in HIV-infected patients perhaps because the elevation of transaminases and changes in liver function tests are often associated to HAART or to other possible liver diseases,namely viral hepatitis and non-alcoholic steatohepatitis. The diagnosis may be underestimated. There are no specific recommendations available for the treatment of HIV-associated AIH although the immunosupression with slower tapering seems the most reasonable approach.展开更多
Drug induced liver injury(DILI) is a common condition of increasing incidence. Many environmental and genetic factors are involved in its pathogenesis,and immunological mechanisms are also thought to contribute to the...Drug induced liver injury(DILI) is a common condition of increasing incidence. Many environmental and genetic factors are involved in its pathogenesis,and immunological mechanisms are also thought to contribute to the development and severity of DILI. This review summarizes current understanding of the immunological pathogenesis of DILI and discusses the perspective for clinical applications.展开更多
Hepatitis C virus(HCV) is an important etiologic agent of hepatitis and a major cause of chronic liver infection that often leads to cirrhosis, fibrosis and hepatocellular carcinoma. Although, HCV is a hepatotropic vi...Hepatitis C virus(HCV) is an important etiologic agent of hepatitis and a major cause of chronic liver infection that often leads to cirrhosis, fibrosis and hepatocellular carcinoma. Although, HCV is a hepatotropic virus, there is strong evidence that HCV could replicate extrahepatic in the gastrointestinal tissue which could serve as a reservoir for HCV. The outcome of HCV infection depends mainly on the host innate and adaptive immune responses. Innate immunity against HCV includes mainly nuclear factor cells and activation of IFN-related genes. There is an immunologic link between the gut and the liver through a population of T-cells that are capable of homing to both the liver and gut via the portal circulation. However, little is known on the role of Gut immune response in HCV. In this review we discussed the immune regulation of Gut immune cells and its association with HCV pathogenesis, various outcomes of anti-HCV therapy, viral persistence and degree of liver inflammation. Additionally, we investigated the relationship between Gut immune responses to HCV and IL28Bgenotypes, which were identified as a strong predictor for HCV pathogenesis and treatment outcome after acute infection.展开更多
The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the...The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin(IL)-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.展开更多
Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte an...Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte antigen(CTLA)-4/B7 interaction(using CTLA-4Ig) and the CD40/CD40 L interaction(using anti-CD40 L antibodies) prevents T cell mediated autoimmune diseases, transplant rejection and graft vs host disease in experimental models. Moreover, CTLA-4Ig is in clinical use to treat rheumatoid arthritis(abatacept) and to prevent rejection of renal transplants(belatacept). Under certain experimental conditions, this treatment can even result in tolerance. Surprisingly, the underlying mechanisms of immune modulation are still not completely understood. We here discuss the evidence that costimulation blockade differentially affects effector T cells(Teff) and regulatory T cells(Treg). The latter are required to control inappropriate and unwanted immune responses, and their activity often contributes to tolerance induction and maintenance. Unfortunately, our knowledge on the costimulatory requirements of Treg cells is very limited. We therefore summarize the current understanding ofthe costimulatory requirements of Treg cells, and elaborate on the effect of anti-CD40 L antibody and CTLA-4Ig treatment on Treg cell activity. In this context, we point out that the outcome of a treatment aiming at blocking the CD28/CTLA-4/B7 costimulatory interaction can vary with dosing, timing and underlying immunopathology.展开更多
The prevalence of allergic diseases including atopic dermatitis,asthma,allergic rhinitis(AR)and food allergy is increasing worldwide and they cause a big economic and social burden.Understanding of reasons thatcontrib...The prevalence of allergic diseases including atopic dermatitis,asthma,allergic rhinitis(AR)and food allergy is increasing worldwide and they cause a big economic and social burden.Understanding of reasons thatcontribute to the etiology of allergic diseases as well as new treatment approaches are very important for the follow-up and prevention of these diseases.In recent years,probiotics seem to be promising for allergic diseases.The effect of probiotics in the prevention and treatment of eczema is more extensively studied,but little is known about the association of the microbial flora of the host and allergic airway diseases and the efficacy of probiotics in decreasing the symptoms of patients with asthma and rhinitis.Hitherto,there is no strong evidence for use of probiotics in the treatment of eczema;however,administration of probiotics in breastfeeding mothers in the prenatal period and infants in the postnatal period can be accepted as a safe and helpful option in the prevention of eczema.In contrast,there is not yet reliable evidence or recommendations on use of probiotics for the prevention or treatment of asthma,AR,food allergy,and anaphylaxis currently.More standardized studies should be performed with different strains of probiotics to evaluate the protective and therapeutic effects of probiotics on other allergic diseases as well as eczema.In this review,the relationship between allergy and probiotics is handled in the light of current literature.展开更多
Autoimmunity is believed to develop when genetically predisposed individuals undergo epigenetic modifications in response to environmental factors.Recent advances in the understanding of epigenetic mechanisms suggest,...Autoimmunity is believed to develop when genetically predisposed individuals undergo epigenetic modifications in response to environmental factors.Recent advances in the understanding of epigenetic mechanisms suggest,in autoimmune diseases,a multi-step process involving environmental factors(e.g.,drugs,stress) and endogenous factors(e.g.,cytokines,gender),both leading to the deregulation of the epigenetic machinery(DNA methylation,histone modifications,mi RNA),that in turn specifically affects the immune system and/or the target organ(s).Such effect is reinforced in those patients with risk variants mapping to epigenetically-controlled regulators of immune cells.As a consequence,autoreactive lymphocytes and autoantibodies are produced leading to the development of the autoimmune disease.Potential new therapeutic strategies and biomarkers are also addressed.展开更多
AIM: To study the effect of blocking the eo-2 pathwayon the development and severity of experimental autoimmune encephalomyelitis(EAE). METHODS: We produced m Ab directed against eo-2,named D8. MOG35-55 induced-EAE mi...AIM: To study the effect of blocking the eo-2 pathwayon the development and severity of experimental autoimmune encephalomyelitis(EAE). METHODS: We produced m Ab directed against eo-2,named D8. MOG35-55 induced-EAE mice were dailyintravenously injected with either 25 μg or 100 μg D8,or with vehicle control alone [phosphate-buffered saline(PBS)], starting from day 0 post immunization and weremonitored for EAE clinical score(n = 10 in each group).Mice were sacrificed on day 58 and their sera were assessed for the presence of anti-myelin oligodendrocyteglycoprotein(anti-MOG) antibodies autoantibodies, aswell as for the profile of pro-inflammatory cytokines andchemokines. Histological analysis of brain sections wasperformed by hematoxylin and eosin staining.RESULTS: Daily treatment of EAE induced mice with D8 significantly decreased the severity of EAE symptoms. Treatment with both concentrations of D8 ameliorated EAE symptoms compared to PBS treated mice, starting from day 42 post immunization(0.89 ± 0.35 in D8 25 μg and D8 100 μg treated groups vs 2.11 ± 0.38 in the PBS treated group, P = 0.03). A significant improvement in EAE clinical score compared to total Ig G treated mice was observed with the higher concentration of D8(0.81 ± 0.38 in D8 100 μg treated group vs 2.11 ± 0.31 in Ig G1 treated group, on day 56 post immunization, P = 0.04). D8 treated mice with EAE did not significantly exhibit lower sera levels of anti-MOG autoantibodies compared to Ig G-treated mice. However, they expressed lower sera levels of the pro-inflammatory cytokines: tumor necrosis factor(7.8 ± 0.2 pg/m L in D8 100 μg treated mice vs 19.9 ± 3.4 pg/m L in Ig G treated mice, P = 0.005) and interferon-gamma(1.4 ± 0.6 pg/m L in D8 100 μg treated mice vs 3.6 ± 0.4 pg/m L in Ig G treated mice, P = 0.02), as well as reduced levels of the chemokine macrophage chemoattractant protein-1(27.2 ± 3.1 pg/m L in D8 100 μg treated mice vs 63.7 ± 12.3 pg/m L in Ig G treated mice, P = 0.03). These findings indicate that blocking the eo-2 pathway in EAE may affect not only eosinophil infiltration into the central nervous system(CNS), but also have an effect on monocytes and T cells, but not humoral, mediated responses. Histological analysis of the brains of D8 treated mice with EAE support that this treatment decreases immune cells infiltrates in the CNS.CONCLUSION: Taken together, these findings suggest a role for eo-2 in EAE pathogenesis and consequentially may support a therapeutic potential of anti-eo-2 neutralizing m Ab in multiple sclerosis.展开更多
文摘The methods and strategies used to screen for syphilis and to confirm initially reactive results can vary significantly across clinical laboratories.While the performance characteristics of these different approaches have been evaluated by multiple studies,there is not,as of yet,a single,universally recommende dalgorithm for syphilis testing.To clarify the currently available options for syphilis testing,this update will summarize the clinical challenges to diagnosis,review the specific performance characteristics of treponemal and non-treponemal tests,and finally,summarize select studies published over the past decade which have evaluated these approaches.Specifically,this review will discuss the traditional and reverse sequence syphilis screening algorithms commonly used in the United States,alongside a discussion of the European Centre for Disease Prevention and Control syphilis algorithm.Ultimately,in the United States,the decision of which algorithm to use is largely dependent on laboratory resources,the local incidence of syphilis and patient demographics.
基金Supported by Grant 24590955 for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology,Japan to Kanda T
文摘The average age of hepatitis C virus(HCV)-infected individuals is becoming increasingly higher in Japan and steps should be taken to treat older individuals infected with HCV. Until an interferon-free regimen becomes available, peginterferon plus ribavirin will play a critical role in the treatment. The perception that older HCVinfected patients may be at higher risk than younger patients for adverse events from peginterferon plus ribavirin treatment but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials. A recent genomewide association study revealed that interleukin-28B(IL28B) genotype closely correlates with the treatment response against HCV. The relationship of IL28 B genotype with the treatment response in older HCV-infected patients is also unknown. In this review, we focused on the treatment response in older patients infected with HCV and the effects of IL28 B genotype. IL28 B major genotype is a useful predictor of sustained virological response in the interferon-including treatment of older patients infected with HCV. It also seems useful for avoiding adverse events, although the mechanisms ofthe effects of IL28 B genotype on the treatment outcome are still poorly understood and are currently under investigation. Further studies will be needed.
基金Supported by Grant INFR-2015-253812 from El Consejo Nacional de Ciencia y Tecnología(CONACyT)
文摘Sj?gren's syndrome(SS) is a systemic autoimmune disease that affects primarily the lacrimal and salivary glands. In addition to a systemic autoimmune response directed against ubiquitous antigens(such as Ro and La antigens),patients with SS mount a localized response that affects the epithelial component of exocrine glands leading to the establishment of a destructive inflammatory infiltrate comprised of activated T and B cells. Local chemokine and cytokine production drive the recruitment and local activation of immune cells that cause injury to acinar cells. CD4 T cells with different functional differentiation programs including Th1(IFN-γ),Th2(IL-13,IL-4) and Th17(IL-17,IL-21,IL-22) as well as diverse cytokine signaling pathways,are involved at the initiation,perpetuation,and progression of the disease. Which factors initiate this response and allow it to become chronic are unknown. Proposed mechanisms include viral infections and acinar cell apoptosis. Moreover risk-conferring genetic variants,probably through the facilitation of innate and adaptive immune activation,most certainly contribute to the creation of an underlying environment that fosters tolerance loss and facilitates perpetuation of the autoimmune response. In this review,we describe the mechanisms through which the immune response causes SS and emphasize the pathways that are amenable of being targeted with therapeutic purposes.
文摘Immune regulation of aggressive tumor growth is often outpaced by tumor up-regulation of ligands that inhibit effector immune responses through the activation of immune checkpoints. A few of such checkpoints include programmed death-1(PD-1), cytotoxic T lymphocyte associated antigen-4(CTLA-4), lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, Glucocorticoid-induced TNFR family-related receptor(GITR), and killer cell immunoglobulin like receptor. With the exception of GITR, after binding to their respective ligands these checkpoints induce down-modulation of immune responses to prevent autoimmunity. However, such immune mechanisms are co-opted by tumors to allow rapid tumor cell proliferation. Pre-clinical studies in antibody blockade of PD-1 and CTLA-4 have led to promising augmentation of effector immune responses in murine tumor models, and human antibodies against PD-1 and CTLA-4 alone or in combination have demonstrated tumor regression in clinical trials. The development of immune checkpoint blockade as a potential future immunotherapy has led to increasing interest in combining treatment modalities. Combination checkpoint blockade with chemotherapy and radiation therapy has shown synergistic effects in pre-clinical and clinical studies, and combination checkpoint blockade with bacterial vaccine vectors have produced increased effector immune responses in pre-clinical models. The future of immune checkpoint blockade may be as a powerful adjuvant alongside the current standard of care.
基金Supported by A Grant-in-Aid for Scientific Research from the Ministry of Education,Science,Sports,and Culture(MEXT)of JapanA Grant-in-Aid for AIDS Research from the Ministry of Health,Labor,and Welfare of Japan+1 种基金The Scholarship for the International Priority Graduate Programs,to Hasan Z and Kamori DAdvanced Graduate Courses for International Students(Doctoral Course),MEXT,Japan,to Hasan Z and Kamori D
文摘Viral protein U(Vpu) is an accessory protein associated with two main functions important in human immunodeficiency virus type 1(HIV-1) replication and dissemination; these are down-regulation of CD4 receptor through mediating its proteasomal degradation and enhancement of virion release by antagonizing tetherin/BST2. It is also well established that Vpu is one of the most highly variable proteins in the HIV-1 proteome. However it is still unclear what drives Vpu sequence variability, whether Vpu acquires polymorphisms as a means of immune escape, functional advantage, or otherwise. It is assumed that the host-pathogen interaction is a cause of polymorphic phenotype of Vpu and that the resulting functional heterogeneity of Vpu may have critical significance in vivo. In order to comprehensively understand Vpu variability, it is important to integrate at the population level the genetic associationapproaches to identify specific amino acid residues and the immune escape kinetics which may impose Vpu functional constraints in vivo. This review will focus on HIV-1 accessory protein Vpu in the context of its sequence variability at population level and also bring forward evidence on the role of the host immune responses in driving Vpu sequence variability; we will also highlight the recent findings that illustrate Vpu functional implication in HIV-1 pathogenesis.
文摘Five major porcine coronaviruses(COVs)have been identified which cause severe gastrointestinal(GI)and respiratory disease in pigs.They include transmissible gastroenteritis(TGEV),porcine epidemic diarrhea virus(PEDV),porcine deltacoronavirus,porcine respiratory coronavirus,and porcine hemagglutinating encephalomyelitis.These diseases,especially TGEV and PEDV,have caused epidemics in Europe,Asia,and the Americas over the past 50 years,causing significant economic losses to swine producers.As pigs are a major protein source worldwide there is great interest in understanding,controlling,and preventing these diseases.These diseases have no cure,and current vaccines are not fully protective.On-farm prevention and biosecurity are difficult to enforce and have not stopped the spread of these diseases between herds.Recent advances in the immunology of porcine COVs has revealed that the immune response to porcine COVs shares many similarities with the response to human COVs,leading to increased interest in pigs as models for human disease.Highlights of these advances include the key role of local antigen presenting cells in the gastrointestinal tract in stimulating a protective immune response.This understanding has lead to new proposed vaccines.Advances in the understanding of the ways the viruses evade and degrade the host immune system have also lead to novel proposed therapies.Many of these therapies are in the early development stages,as researchers attempt to create efficacious,cost-effective,and practical therapies for these diseases.
文摘Free radicals(reactive oxygen species,superoxides and hydroxyl radicals)lead to the development of oxidative stress because of imbalance in the amount of antioxidants.Continued development of oxidative stress leads to chronic diseases in humans.The instability in the antioxidant activities and accumulation of oxidative stress due to free radicals may occur in diseases like inflammatory bowel disease(IBD).Antioxidants are substances that inhibit or delay the mechanism of oxidation of molecules mediated by free radicals and also transform into lesseractive derivatives.Probiotics are defined as live microorganisms that show beneficial effects on inflamed intestine and balance the inflammatory immune responses in the gut.Probiotic strains have been reported to scavenge hydroxyl radicals and superoxide anions that are abundantly produced during oxidative stress.The most widely studied probiotic strains are Streptococcus,Bifidobacterium and Lactobacillus.Probiotics cultured in broth have shown some amount of antioxidant activities.Fermented milk and soy milk,which possess starter microorganisms(probiotics),tends to increase the antioxidant activities manyfold.This review aims to discuss the in vivo and in vitro antioxidant activities of specific probiotics with various assays with respect to IBD.
基金Supported by The National Science Foundation grant MCB-08-42725National Institutes of Health shared resources Grant No.P30CA047904 to the University of Pittsburgh Cancer Instituteinternal funding from the School of Medicine and Department of Immunology
文摘There is a major transformation in gene expression between mature B cells(including follicular,marginal zone,and germinal center cells) and antibody secreting cells(ASCs),i.e.,ASCs,(including plasma blasts,splenic plasma cells,and long-lived bone marrow plasma cells). This significant change-over occurs to accommodate the massive amount of secretory-specific immunoglobulin that ASCs make and the export processes itself. It is well known that there is an up-regulation of a small number of ASC-specific transcription factors Prdm1(B-lymphocyte-induced maturation protein 1),interferon regulatory factor 4,and Xbp1,and the reciprocal downregulation of Pax5,Bcl6 and Bach2,which maintain the B cell program. Less well appreciated are the major alterations in transcription elongation and RNA processing occurring between B cells and ASCs. The three ELL family members ELL1,2 and 3 have different protein sequences and potentially distinct cellular roles in transcription elongation. ELL1 is involved in DNA repair and small RNAs while ELL3 was previously described as either testis or stem-cell specific. After B cell stimulation to ASCs,ELL3 levels fall precipitously while ELL1 falls off slightly. ELL2 is induced at least 10-fold in ASCs relative to B cells. All of these changes cause the RNA Polymerase Ⅱ in ASCs to acquire different properties,leading to differences in RNA processing and histone modifications.
文摘An important percentage of colorectal cancer(CRC) patients will develop metastasis,mainly in the liver,even after a successful curative resection.This leads to a very high mortality rate if metastasis is not detected early on.Disseminated cancer cells develop from metastatic stem cells(Met SCs).Recent knowledge has accumulated about these cells particularly in CRC,so they may now be tracked from the removed primary tumour.This approach could be especially important in prognosis of metastasis because it is becoming clear that metastasis does not particularly rely on testable driver mutations.Among the many traits supporting an epigenetic amplification of cell survival and self-renewal mechanisms of Met SCs,the role of many immune cell populations present in tumour tissues is becoming clear.The amount of tumour-infiltrating lymphocytes(T,B and natural killer cells),dendritic cells and some regulatory populations have already shown prognostic value or to be correlated with disease-free survival time,mainly in immunohistochemistry studies of unique cell populations.Parallel analyses of these immune cell populations together with Met SCs in the primary tumour of patients,with later follow-up data of the patients,will define the usefulness of specific combinations of both immune and Met SCs cell populations.It is expected that these combinations,together to different biomarkers in the form of an immune score,may predict future tumour recurrences,metastases and/or mortality in CRC.It will also support the future design of improved immunotherapeutic approaches against metastasis.
文摘Pancreatic cancer has an overall 5-year survival rate of less than 5%.Unfortunately,patient survival has not substantially improved in the last couple of decades despite advances in treatment modalities that have been successful in other cancer types.The poor response of pancreatic cancer to therapy is a majo obstacle faced by clinicians.Increasing attention is bein paid to how tumor cells and non-tumor cells influenc each other in the pancreatic tumor microenvironment Tumor-associated macrophages(TAMs)are a highligh in this field because of their vast presence in th tumor microenvironment.TAMs promote angiogenesis metastasis,and suppress the anti-tumor immun response.Here we review the current understandin of the role of TAMs in regulating the progression o pancreatic cancer.
文摘Sézary syndrome(SS) is an aggressive variant of cutaneous T cell lymphoma characterized by the presence of malignant T cells in the skin, peripheral blood and lymph nodes. The tumoral population typically displays a CD3+ CD4+ CD45RO+ memory T cell phenotype. We report a case of SS with an aberrant CD56+ immunophenotype. This patient presented with a generalized erythroderma and palpable small axillary lymph nodes.SS(stage IVA) was diagnosed on histological criteria and by the detection of a major T cell clone in skin and blood, an elevated CD4/CD8 T cell ratio and Sézary cells count > 1000/mm3. Beside the Sézary cell marker KIR3DL2, immunostainings revealed that two third of the malignant cells expressed CD56 but no other natural killer(NK) cell marker such as CD16, CD160 or NKp46. This atypical expression was not linked to an activation-dependent process and remained stable during the time course of the disease. No loss of the panT-cell markers CD2, CD3 or CD4 was detected while a complete down-modulation of CD26 was observed. Despite several lines of treatment, no durable amelioration was observed and patient died after 10 mo of follow-up. Because this CD4+ CD56+ SS case is the only one reported so far, the functional significance of CD56 expression remained difficult to assess in terms of aggressiveness and prognosis.
文摘Ulcerative colitis and Crohn's disease, collectively termed the inflammatory bowel diseases(IBD), are chronic inflammatory disorders of the gastrointestinal tract. A "dysbiotic" relationship between the commensal gut flora and the intestinal mucosa-associated immune system has been at the core of the pathogenesis of these conditions. Probiotics are "good bacteria" with the ability to benefit the health of the host and their therapeutic application has been studied in IBD. The theoretical basis for such utilization relies upon the ability of probiotic microorganisms to interfere with the dysregulated homeostasis that takes place in IBD and restore the immune-bacterial interaction at the intestinal mucosa. Proposed mechanisms of action include the reconstitution of altered flora composition, enhancement of the integrity of the epithelial barrier, promotion of tolerogenic action by dendritic cells, strengthening of the defensive mechanisms of the innate immunity, and the suppression of pro-inflammatory adaptive immune responses. Despite this abundance of supporting experimental evidence, clinical application of probiotics in IBD has been disappointing. Possible explanations for such discrepancy include the great diversity of microorganisms that fall under the definition of probiotics, the lack of standardization of dosages and administration schemes, the heterogeneity between clinical trials, and the inclusion in the treatment arms of patients with a large variety of clinical phenotypes. Addressing these important issues will be critical for the optimal usage of probiotic-based therapies for patients with IBD.
文摘Liver disease has recently been described as an important cause of morbidity and mortality in patients infected with human immunodeficiency virus(HIV). Liver test changes are useful surrogates of the burden of liver disease. Previous studies have shown that transaminase elevations are frequent among these patients. The cause of those changes is harder to establish in HIV-patients. We present a 61-year-old caucasian male,diagnosed with HIV type 1 infection since 1998,under highly active antiretroviral treatment(HAART),with virological suppression and immunological recovery. He presented in a follow-up laboratory workup high values of transaminases,arthralgia at the hip joints and hepatomegaly. Liver function tests were normal. The antibodies to hepatitis viruses were negative. However,autoimmune study and liver biopsy were compatible with autoimmune hepatitis(AIH). The AIH is a rare di-agnosis in HIV-infected patients perhaps because the elevation of transaminases and changes in liver function tests are often associated to HAART or to other possible liver diseases,namely viral hepatitis and non-alcoholic steatohepatitis. The diagnosis may be underestimated. There are no specific recommendations available for the treatment of HIV-associated AIH although the immunosupression with slower tapering seems the most reasonable approach.
文摘Drug induced liver injury(DILI) is a common condition of increasing incidence. Many environmental and genetic factors are involved in its pathogenesis,and immunological mechanisms are also thought to contribute to the development and severity of DILI. This review summarizes current understanding of the immunological pathogenesis of DILI and discusses the perspective for clinical applications.
基金Supported by Egyptian Government Scholarship for Helal HettaMerck Investigator Initiated Studies(IIS)IISP,No.40458(Shata)
文摘Hepatitis C virus(HCV) is an important etiologic agent of hepatitis and a major cause of chronic liver infection that often leads to cirrhosis, fibrosis and hepatocellular carcinoma. Although, HCV is a hepatotropic virus, there is strong evidence that HCV could replicate extrahepatic in the gastrointestinal tissue which could serve as a reservoir for HCV. The outcome of HCV infection depends mainly on the host innate and adaptive immune responses. Innate immunity against HCV includes mainly nuclear factor cells and activation of IFN-related genes. There is an immunologic link between the gut and the liver through a population of T-cells that are capable of homing to both the liver and gut via the portal circulation. However, little is known on the role of Gut immune response in HCV. In this review we discussed the immune regulation of Gut immune cells and its association with HCV pathogenesis, various outcomes of anti-HCV therapy, viral persistence and degree of liver inflammation. Additionally, we investigated the relationship between Gut immune responses to HCV and IL28Bgenotypes, which were identified as a strong predictor for HCV pathogenesis and treatment outcome after acute infection.
基金Supported by Fondation de France (to Apetoh L and Rivera Vargas T)the Association pour la recherche sur le cancer (to Apetoh L)+6 种基金the Institut Mérieux (to Apetoh L)the Conseil Régional de Bourgogne (to Apetoh L)the FEDER,the Agence Nationale de la Recherche,No.ANR-13-JSV3-0001 (to Apetoh L) and No.ANR-11-LABX-0021the ARSEP (to Apetoh L)the Ligue Régionale contre le cancer Comité Grand-Est (to Apetoh L)the European Commission (Marie Curie Fellowship PCIG10-GA-2011-303719)the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No.677251)
文摘The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin(IL)-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.
文摘Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte antigen(CTLA)-4/B7 interaction(using CTLA-4Ig) and the CD40/CD40 L interaction(using anti-CD40 L antibodies) prevents T cell mediated autoimmune diseases, transplant rejection and graft vs host disease in experimental models. Moreover, CTLA-4Ig is in clinical use to treat rheumatoid arthritis(abatacept) and to prevent rejection of renal transplants(belatacept). Under certain experimental conditions, this treatment can even result in tolerance. Surprisingly, the underlying mechanisms of immune modulation are still not completely understood. We here discuss the evidence that costimulation blockade differentially affects effector T cells(Teff) and regulatory T cells(Treg). The latter are required to control inappropriate and unwanted immune responses, and their activity often contributes to tolerance induction and maintenance. Unfortunately, our knowledge on the costimulatory requirements of Treg cells is very limited. We therefore summarize the current understanding ofthe costimulatory requirements of Treg cells, and elaborate on the effect of anti-CD40 L antibody and CTLA-4Ig treatment on Treg cell activity. In this context, we point out that the outcome of a treatment aiming at blocking the CD28/CTLA-4/B7 costimulatory interaction can vary with dosing, timing and underlying immunopathology.
文摘The prevalence of allergic diseases including atopic dermatitis,asthma,allergic rhinitis(AR)and food allergy is increasing worldwide and they cause a big economic and social burden.Understanding of reasons thatcontribute to the etiology of allergic diseases as well as new treatment approaches are very important for the follow-up and prevention of these diseases.In recent years,probiotics seem to be promising for allergic diseases.The effect of probiotics in the prevention and treatment of eczema is more extensively studied,but little is known about the association of the microbial flora of the host and allergic airway diseases and the efficacy of probiotics in decreasing the symptoms of patients with asthma and rhinitis.Hitherto,there is no strong evidence for use of probiotics in the treatment of eczema;however,administration of probiotics in breastfeeding mothers in the prenatal period and infants in the postnatal period can be accepted as a safe and helpful option in the prevention of eczema.In contrast,there is not yet reliable evidence or recommendations on use of probiotics for the prevention or treatment of asthma,AR,food allergy,and anaphylaxis currently.More standardized studies should be performed with different strains of probiotics to evaluate the protective and therapeutic effects of probiotics on other allergic diseases as well as eczema.In this review,the relationship between allergy and probiotics is handled in the light of current literature.
基金Supported by The"Région Bretagne",the"Association Franaise Gougerot-Sjgren et des Syndromes Secs"the"Institut Franais pour la Recherche Odontologique"+1 种基金the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115565,resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme(FP7/2007-2013)EFPIA companies’ in-kind contribution
文摘Autoimmunity is believed to develop when genetically predisposed individuals undergo epigenetic modifications in response to environmental factors.Recent advances in the understanding of epigenetic mechanisms suggest,in autoimmune diseases,a multi-step process involving environmental factors(e.g.,drugs,stress) and endogenous factors(e.g.,cytokines,gender),both leading to the deregulation of the epigenetic machinery(DNA methylation,histone modifications,mi RNA),that in turn specifically affects the immune system and/or the target organ(s).Such effect is reinforced in those patients with risk variants mapping to epigenetically-controlled regulators of immune cells.As a consequence,autoreactive lymphocytes and autoantibodies are produced leading to the development of the autoimmune disease.Potential new therapeutic strategies and biomarkers are also addressed.
文摘AIM: To study the effect of blocking the eo-2 pathwayon the development and severity of experimental autoimmune encephalomyelitis(EAE). METHODS: We produced m Ab directed against eo-2,named D8. MOG35-55 induced-EAE mice were dailyintravenously injected with either 25 μg or 100 μg D8,or with vehicle control alone [phosphate-buffered saline(PBS)], starting from day 0 post immunization and weremonitored for EAE clinical score(n = 10 in each group).Mice were sacrificed on day 58 and their sera were assessed for the presence of anti-myelin oligodendrocyteglycoprotein(anti-MOG) antibodies autoantibodies, aswell as for the profile of pro-inflammatory cytokines andchemokines. Histological analysis of brain sections wasperformed by hematoxylin and eosin staining.RESULTS: Daily treatment of EAE induced mice with D8 significantly decreased the severity of EAE symptoms. Treatment with both concentrations of D8 ameliorated EAE symptoms compared to PBS treated mice, starting from day 42 post immunization(0.89 ± 0.35 in D8 25 μg and D8 100 μg treated groups vs 2.11 ± 0.38 in the PBS treated group, P = 0.03). A significant improvement in EAE clinical score compared to total Ig G treated mice was observed with the higher concentration of D8(0.81 ± 0.38 in D8 100 μg treated group vs 2.11 ± 0.31 in Ig G1 treated group, on day 56 post immunization, P = 0.04). D8 treated mice with EAE did not significantly exhibit lower sera levels of anti-MOG autoantibodies compared to Ig G-treated mice. However, they expressed lower sera levels of the pro-inflammatory cytokines: tumor necrosis factor(7.8 ± 0.2 pg/m L in D8 100 μg treated mice vs 19.9 ± 3.4 pg/m L in Ig G treated mice, P = 0.005) and interferon-gamma(1.4 ± 0.6 pg/m L in D8 100 μg treated mice vs 3.6 ± 0.4 pg/m L in Ig G treated mice, P = 0.02), as well as reduced levels of the chemokine macrophage chemoattractant protein-1(27.2 ± 3.1 pg/m L in D8 100 μg treated mice vs 63.7 ± 12.3 pg/m L in Ig G treated mice, P = 0.03). These findings indicate that blocking the eo-2 pathway in EAE may affect not only eosinophil infiltration into the central nervous system(CNS), but also have an effect on monocytes and T cells, but not humoral, mediated responses. Histological analysis of the brains of D8 treated mice with EAE support that this treatment decreases immune cells infiltrates in the CNS.CONCLUSION: Taken together, these findings suggest a role for eo-2 in EAE pathogenesis and consequentially may support a therapeutic potential of anti-eo-2 neutralizing m Ab in multiple sclerosis.
