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外周血CD4^(+)PD-1^(+)Tcells及CD4^(+)T淋巴细胞ATP含量与复发性卵巢癌疗效的相关性分析
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作者 李慧芬 《实用妇科内分泌电子杂志》 2023年第27期24-26,共3页
目的 探讨外周血CD4^(+)程序性细胞死亡受体-1(PD-1)^(+)T cells及CD4^(+)T淋巴细胞三磷酸腺苷(ATP)含量与复发性卵巢癌疗效的相关性。方法 选取30例复发性卵巢癌患者为复发组,30例未复发卵巢癌患者为非复发组;另选取30名同期体检健康... 目的 探讨外周血CD4^(+)程序性细胞死亡受体-1(PD-1)^(+)T cells及CD4^(+)T淋巴细胞三磷酸腺苷(ATP)含量与复发性卵巢癌疗效的相关性。方法 选取30例复发性卵巢癌患者为复发组,30例未复发卵巢癌患者为非复发组;另选取30名同期体检健康者作为对照组。评估外周血CD4^(+)PD-1^(+)T cells及CD4^(+)T淋巴细胞ATP含量与复发性卵巢癌疗效的相关性。结果 复发组和非复发组的CD4^(+)PD-1^(+)T cells较对照组明显升高(P<0.05)。复发组和非复发组的CD4^(+)T淋巴细胞ATP含量较对照组明显降低(P<0.05)。复发组治疗后CD4^(+)PD-1^(+)Tcells显著低于治疗前(P<0.05),治疗后CD4^(+)T淋巴细胞ATP含量显著高于治疗前(P<0.05)。CD4^(+)PD-1^(+)T cells与复发性卵巢癌疗效成负相关(r=-0.393,P=0.039),CD4^(+)T淋巴细胞ATP含量与复发性卵巢癌疗效成正相关(r=0.449,P=0.031)。结论 复发性卵巢癌患者外周血CD4^(+)PD-1^(+)T cells及CD4^(+)T淋巴细胞ATP含量与疗效密切相关。 展开更多
关键词 复发性卵巢癌 cd4^(+)PD-1^(+)t cells cd4^(+)t淋巴细胞AtP含量
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MBD2 promotes Th2 differentiation in ovalbumin-induced CD4+T cells
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作者 QILU PAN YAN JIANG +8 位作者 LINQIAO LI XIAOJING DU QIAN HAN FEIXIANG LING ROU LI SHUYUAN CHU LIN MAI JIANWEI HUANG LIBING MA 《BIOCELL》 SCIE 2023年第11期2495-2502,共8页
Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate t... Introduction:Allergen-specific CD4+T cells play a central role in autoimmune disorders,allergies and asthma,with Th2-type immunity being the typical functional response of CD4+T cells.This study aimed to investigate the role of MBD2 in regulating Th2 cell differentiation.Methods:Splenic mononuclear cells were extracted from C57BL/6 mice,and CD4+T cells were isolated using magnetic beads and confirmed through flow cytometry.Lentivirus was employed to construct MBD2-silenced CD4+T cells.In vitro experiments were performed to treat splenogenic mononuclear cells and CD4+T cells with Ovalbumin(OVA),and Th2 cell ratios and IL-4 levels were assessed using flow cytometry and ELISA.Results:The purity of the isolated CD4+T cells was 95.73%,confirming successful isolation of primary CD4+T cells.Compared to the control group,the Th2 cell ratio exhibited an increase in the Th2-induced group.Treatment with 5-Aza(concentrations,1-100μM)promoted Th2 cell differentiation and increased IL-4 levels.Notably,when combined with Th2 induction and 10μM 5-Aza treatment,silencing MBD2 further amplified Th2 cell ratios and elevated IL-4 levels in cell supernatants.Furthermore,OVA(concentration,200μg/mL)induced the differentiation of CD4+T cells into Th2 cells and increased IL-4 secretion.Interestingly,silencing MBD2 significantly increased the Th2 cell ratio and IL-4 levels in OVA-treated CD4+T cells.Conclusion:In summary,OVA promoted CD4+T cell differentiation into Th2 cells and enhanced IL-4 levels.MBD2 was identified as a mediator of Th2 cell differentiation in splenic-derived CD4+T cells,influenced by OVA or 5-Aza treatment. 展开更多
关键词 5-AZA MBD2 cd4+t cells th2 cells OVALBUMIN
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Peripheral CD4^(+)CD8^(+) double positive T cells:A potential marker to evaluate renal impairment susceptibility during systemic lupus erythematosus
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作者 Kai Chang Wanlin Na +4 位作者 Chenxia Liu Hongxuan Xu Yuan Liu Yanyan Wang Zhongyong Jiang 《The Journal of Biomedical Research》 CAS CSCD 2023年第1期59-68,共10页
Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^... Lupus nephritis(LN) has a high incidence in systemic lupus erythematosus(SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4^(+)CD8^(+)double positive T(DPT) lymphocytes and LN. The study included patients with SLE without renal impairment(SLE-NRI), LN, nephritic syndrome(NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group(t=4.012, P<0.001), NS group(t=3.240,P=0.001), and nephritis group(t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times(95% confidence interval, 2.115–12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion. 展开更多
关键词 cd4^(+)CD8^(+)double positive t cells lupus nephritis SUSCEPtIBILItY systemic lupus erythematosus
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Advanced Glycation End Products Promote Differentiation of CD4^+ T Helper Cells toward Pro-inflammatory Response 被引量:5
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作者 韩晓群 龚作炯 +5 位作者 徐三清 李汛 王立坤 伍仕敏 吴建红 杨华芬 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第1期10-17,共8页
This study investigated the effect of advanced glycation end products(AGEs) on differentiation of na ve CD4+T cells and the role of the receptor of AGEs(RAGE) and peroxisome proliferator-activated receptors(PPAR... This study investigated the effect of advanced glycation end products(AGEs) on differentiation of na ve CD4+T cells and the role of the receptor of AGEs(RAGE) and peroxisome proliferator-activated receptors(PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin(BSA) with glucose. Human na ve CD4+T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin(sh) RNA knock-down experiment, na ve CD4+T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-XTM293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4+T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T(Treg) cells was determined by a [3H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from na ve CD4+T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in na ve CD4+T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4+T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα; PPARγ agonist, PGJ2, inhibited the effect of AGEs on na ve CD4+T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4+T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity. + 展开更多
关键词 DIABEtES advanced glycation end products cd4t cell subsets pro-inflammatory re-sponse
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An Association between Immunosenescence and CD4^+CD25^+ Regulatory T Cells: A Systematic Review 被引量:10
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作者 LING WANG YAN XIE LI-JING ZHU TING-TING CHANG YAN-QING MAO JIE LI 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2010年第4期327-332,共6页
Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The a... Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8+ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^+CD25^+ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4+ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals. 展开更多
关键词 Aging IMMUNOSENESCENCE cd4^+CD25^+ t cell treg Case-control studies Cohort studies Cross-sectional studies
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All-transRetinoic Acid Regulates Th1/Th2 Balance in CD4+T cells When GATA-3 is Deficient 被引量:6
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作者 ZHU Yan Feng HU Jia Zhe +2 位作者 ZHAO Pin Nan LIU Lin Xi and LI Yun 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2013年第9期774-777,共4页
The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balanc... The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid (ATRA) on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4+ T cells and normal CD4+ T were treated for 48 h with or without ATRA. 展开更多
关键词 GAtA cell th All-transRetinoic Acid Regulates th1/th2 Balance in cd4+t cells When GAtA-3 is Deficient CD
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Analysis of CD4^+CD25^+ Regulatory T Cells and Foxp3 mRNA in the Peripheral Blood of Patients with Asthma 被引量:15
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作者 薛克营 周咏明 +2 位作者 熊盛道 熊维宁 唐滔 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2007年第1期31-33,共3页
The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible role... The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4^+CD25^+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P〈0.05). Although the CD4^+CD25^+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P〉0.05). As compared with persistent group, exacerbation group had lower CD4^+CD25^+ Treg ratio and Foxp3 mRNA (P〈0.05). It was indicated that the decrease of CD4^+CD25^+ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma. 展开更多
关键词 AStHMA peripheral blood mononuclear cells cd4^+CD25^+ regulatory t cells Foxp3 mRNA
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Depletion of CD4^+CD25^+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma 被引量:9
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作者 Yi-Ling Chen Jung-Hua Fang +1 位作者 Ming-Derg Lai Yan-Shen Shan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第38期5797-5809,共13页
AIM: To elucidate the distribution of CD4^+CD25^+ regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4^+CD25^+ Tregs. METHODS: Fe... AIM: To elucidate the distribution of CD4^+CD25^+ regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4^+CD25^+ Tregs. METHODS: Female ICR mice were garaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4^+CD25^+ Tregs were intraperitoneally depleted with monoclonal antibody PC61. These mice were divided into BaP-only, BaP + IgG, BaP + PC61, and control groups. The forestomach of mice was dissected for histological analysis, and tunnel test was performed for apoptosis of tumor cells. CD4^+CD25^+ Tregs were sorted from different lymphoid tissues and expression of Foxp3, IL-10, and chemokine receptors was analyzed by flow cytometry, semi-quantitative and veal-time polymerase chain reaction. RESULTS: The mice gavaged with only BaP showed increased forestomach papilloma and carcinoma at wk 16 and 32. The proportion of CD4^+CD25^+ Tregs was significantly higher in peri-stomach regional lymph nodes than in other lymphoid tissues. These CD4^+CD25^+ Tregs in regional lymph nodes expressed higher levels of Foxp3 and IL-10, enriched in the CD62L-subset, and CCR1 and CCR5 chemokine receptors. In mice gavaged with BaP + PC61, the number of tumor nodules and tumor volume decreased significantly with massive infiltrating cells and apoptosis of tumor cells. In the draining regional lymph nodes, the number of CD4^+CD25^+ Tregs also decreased significantly. CONCLUSION: Inducible and activated CD4^+CD25^+ Tregs in the draining regional lymph nodes suppress host local immunity during tumor growth. Depletion of CD4^+CD25^+ Tregs can promote host local immunity to suppress tumor growth. 展开更多
关键词 cd4^+CD25^+ regulatory t cells Forestomach tumor FOXP3
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Proliferation and Apoptosis of Bone Marrow CD4^+ T Cells in Patients with Aplastic Anemia and Impacts of the Secreted Cytokines on Hematopoietic Stem Cells from Umbilical Cord Blood 被引量:3
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作者 郑邈 孙汉英 +3 位作者 周剑峰 徐慧珍 黄丽芳 刘文励 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第1期37-41,共5页
Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.M... Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy con... 展开更多
关键词 aplastic anemia cd4+ t cell proliferation apoptosis CYtOKINE
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Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+T cells’T helper 17 polarization 被引量:2
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作者 Li-Wei Dong Zhi-Chao Ma +4 位作者 Jiao Fu Bai-Li Huang Fu-Jin Liu Deming Sun Cheng Lan 《World Journal of Gastroenterology》 SCIE CAS 2022年第25期2955-2967,共13页
BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in P... BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells. 展开更多
关键词 Adenosine 2A receptor cd4+t cells t helper 17 polarization Post-infectious irritable bowel syndrome REGULAtION
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Increase of CD4^+CD25^+ T cells in Smad3^(-/-) mice 被引量:3
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作者 Zi-Bing Wang Yu-Fang Cui +7 位作者 Yu-Qing Liu Wei Jin Han Xu Zhu-Jun Jiang Ya-Xin Lu Ying Zhang Xiao-Lan Liu Bo Dong 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第15期2455-2458,共4页
AIM: To investigate the changes of lymphocyte subpopulations, especially CD4^+CD25^ T regulatory cells in Smad3^-/- mice. METHODS: Hematological changes and changes of lymphocyte subpopulations were detected in Sm... AIM: To investigate the changes of lymphocyte subpopulations, especially CD4^+CD25^ T regulatory cells in Smad3^-/- mice. METHODS: Hematological changes and changes of lymphocyte subpopulations were detected in Smad3"/- mice using cell counter and flow cytometry, respectively, and compared to their littermate controls. RESULTS: The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3^-/- mice compared to littermate controls. CD19^+ expressing cells in blood and spleen, and CD8^+ T cells in thymus were all markedly decreased in Smad3^-/- mice. More important, Smad3^-/- mice had an increased population of CD4^+CD25^+ T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes. CONCLUSION: These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3^-/- mice. 展开更多
关键词 cd4^+CD25^+ t cells Lymphocyte subpopulation SMAD3 tGF-β signaling
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Combined TIM-3 and PD-1 blockade restrains hepatocellular carcinoma development by facilitating CD4+ and CD8+T cellmediated antitumor immune responses
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作者 Xu-Sheng Zhang Hong-Cai Zhou +5 位作者 Peng Wei Long Chen Wei-Hu Ma Lin Ding Shi-Cai Liang Ben-Dong Chen 《World Journal of Gastrointestinal Oncology》 SCIE 2023年第12期2138-2149,共12页
BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity... BACKGROUND Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies.However,ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma(HCC)patients due to the complex pathological mechanisms of HCC.AIM To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model,aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.METHODS The levels of PD-1 and TIM-3 on CD4+and CD8+T cells from tumor tissues,ascites,and matched adjacent tissues from HCC patients were determined with flow cytometry.An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody(mAb)and/or anti-PD-1 mAb.Tumor growth in each group was measured.Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors.The percentage of CD4+and CD8+T cells in tissue samples from mice was tested with flow cytometry.The percentages of PD-1+CD8+,TIM-3+CD8+,and PD-1+TIM-3+CD8+T cells was accessed by flow cytometry.The levels of the cytokines including tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),interleukin(IL)-6,and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.RESULTS We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+and CD8+T cells isolated from tumor tissues and ascites of HCC patients.TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight,while combined blockade had more substantial anti-tumor effects than individual treatment.Then we showed that combined therapy increased T cell infiltration into tumor tissues,and downregulated PD-1 and TIM-3 expression on CD8+T cells in tumor tissues.Moreover,combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ,and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues.Thus,we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.CONCLUSION Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+T cell-mediated antitumor immune responses. 展开更多
关键词 Hepatocellular carcinoma t cell immunoglobulin and mucin domain-containing protein 3 Programmed cell death protein 1 cd4+t cells CD8+t cells
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CD4^+CXCR5^+ T cells activate CD27^+IgG^+ B cells via IL-21 in patients with hepatitis C virus infection 被引量:4
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作者 Fan-Yun Kong Bo Feng +4 位作者 Heng-Hui Zhang Hui-Ying Rao Jiang-Hua Wang Xu Cong Lai Wei 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2016年第1期55-64,共10页
BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepa- titis C (CHC) infection have not ... BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepa- titis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation ofIgG+ B cells in CHC patients is not clear. METHODS: The frequency of IgG+ B cells, including CD27-IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circu- lating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The con- centrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system. RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells.CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21. 展开更多
关键词 chronic hepatitis C IgG+ B cells cd4+CXCR5+ t cells
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Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats 被引量:6
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作者 Keying Xue Yongming Zhou +2 位作者 Shengdao Xiong Weining Xiong Dan Li 《Journal of Nanjing Medical University》 2006年第5期292-295,共4页
Objective: To investigate the influence of Danshen Injection on airway inflammation and CD4^+CD25^+ regulatory T cells(CD4^+CD25^+ Tr) of asthmatic rats, and elucidate the possible mechanism of Danshen Inject... Objective: To investigate the influence of Danshen Injection on airway inflammation and CD4^+CD25^+ regulatory T cells(CD4^+CD25^+ Tr) of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods: 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids (BALF) were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain (HE). Flow cytometry was used to detect the CD4^+CD25^+ Tr ratio in peripheral blood mononuclear cells (PBMCs). Results: Total cell, the percentage of lymphocytes, neutrophils and eosinophils (Eos) in BALF of Danshen Injection-treated group were lower than that in asthma group (P〈0.05, P〈0.01). Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^+CD25^+ Tr of asthma group was lower than that of control and Danshen Injection treated group (P〈0.05). Conclusion: Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^+CD25^+ Tr. 展开更多
关键词 Danshen Injection AStHMA airway inflammation cd4^+CD25^+ regulatory t cells
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CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients 被引量:2
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作者 Natalia Laufer Diego Ojeda +6 位作者 María Laura Polo Ana Martinez Héctor Pérez Gabriela Turk Pedro Cahn Norberto Walter Zwirner Jorge Quarleri 《World Journal of Hepatology》 CAS 2017年第25期1073-1080,共8页
AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHO... AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHODS Peripheral mononuclear cells from 24 HIV/HCV(HBVnegative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: AntiCD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), antiNKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L(PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-Fas L(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using Flow Jo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was(6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls(G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1(G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage. 展开更多
关键词 cd4^+ t cell Human immunodeficiency virus/hepatitis C virus-coinfection FIBROSIS BIOMARKER Natural killer cells
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A tale of motor neurons and CD4+ T cells: moving forward by looking back 被引量:1
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作者 Abhirami Kannan Iyer Kathryn J.Jones 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第4期562-565,共4页
Amyotrophic lateral sclerosis (ALS) is a fatal progressive disorder characterized by the selective degeneration of motor neurons (MN). The impact of peripheral immune status on disease progression and MN survival ... Amyotrophic lateral sclerosis (ALS) is a fatal progressive disorder characterized by the selective degeneration of motor neurons (MN). The impact of peripheral immune status on disease progression and MN survival is becoming increasingly recognized in the ALS research field. In this review, we briefly discuss findings from mouse models of peripheral nerve injury and immunodeficiency to understand how the immune system regulates MN survival. We extend these observations to similar studies in the widely used superoxide dismutase 1 (SOD1) mouse model of ALS. Last, we present future hypotheses to identify potential causative factors that lead to immune dysregulation in ALS. The lessons from preceding work in this area offer new exciting directions to bridge the gap in our current understanding of immune mediated neuroprotection in ALS. 展开更多
关键词 amyotrophic lateral sclerosis (ALS) superoxide dismutase 1 (SOD1) immune system SOD1 mice motor neuron cd4 t cells NEUROPROtECtION
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Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions
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作者 Jing Xu Jilong Ren +11 位作者 Kai Xu Minghui Fang Meina Ka Fei Xu Xin Wang Jing Wang Zhiqiang Han Guihai Feng Ying Zhang Tang Hai Wei Li Zheng Hu 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第4期584-590,共7页
Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Curren... Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion. 展开更多
关键词 cd4 t cell genetically edited pig immune rejection major histocompatibility complex II XENOtRANSPLANtAtION
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Isolation and identification of CD4^+CD25^+ regulatory T cells in rat 被引量:1
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作者 Ling Lü Feng Zhang Liyong Pu Chao Jiang 《Journal of Nanjing Medical University》 2006年第4期238-241,共4页
Objective: To establish a stable and high efficient method for collection of CD4^+CD25^+ regulatory T cells from rats in vitro. Methods: CD4^+CD25^+ regulatory T cells were isolated from the rat splenic cells th... Objective: To establish a stable and high efficient method for collection of CD4^+CD25^+ regulatory T cells from rats in vitro. Methods: CD4^+CD25^+ regulatory T cells were isolated from the rat splenic cells through two steps by magic cell sorting (MACS) system. The first step was negative selection of CD4^+T cells by cocktail antibodies and anti-IgG magic microbeads, and the second step was positive selection of CD25^+T cells by anti-CD25 PE and anti-PE magic microbeads. The purity and viability of separated cells were measured by flow cytometry (FACS) and Trypan blue staining. The suppressive ability of seperated cells on the proliferation of CD4^+CD25^- T cells was assessed by cell proliferation assay. Results: The purity of negatively enriched CD4^+ T cells was 79%-87% (83.6%±2.5% ) , and the purity of positively enriched CD4^+CD25^+ T cells was 86%- 93% ( 90.2±1.8% ) with the viability of 92%~95% (92.8% ± 3.4% ). The enriched cells significantly suppressed the proliferation of CD4^+CD25^- T cells in mixed lymphocyte culture (P 〈 0.05). Conclusion: An effective method can be established for enrichment of CD4^+CD25^+ regulatory T cells in two steps by MACS, with satisfied cell purity, viability and function. 展开更多
关键词 magic cell sorting system cd4^+CD25^+ regulatory t cells flow cytometry technique RAtS
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Effect of CD4^+CD25^+ regulatory T cells in the development of anterior chamber-associated immune deviation
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作者 Shu-Xing Ji, Pei-Zeng Yang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2011年第1期19-25,共7页
AIM: To investigate whether CD4(+)CD25(+) regulatory T (Treg) cells play a role in the development of anterior chamber-associated immune deviation (ACAID). METHODS: The dynamic changes in the frequency of CD4(+)D25(+)... AIM: To investigate whether CD4(+)CD25(+) regulatory T (Treg) cells play a role in the development of anterior chamber-associated immune deviation (ACAID). METHODS: The dynamic changes in the frequency of CD4(+)D25(+) T cells, CD4(+)D25(+) FoxP3(+) T cells and CD4(+)CD25(+) PD-1(+) T cells from spleens of mice with ACAID were analyzed by flow cytometry. Foxp3 mRNA expression in purified CD4(+)CD25(+) T cells was analyzed using real-time PCR. The suppressive effect of purified CD4(+)CD25(+) T cells on the proliferation of CD4(+)CD25(-) T cells was evaluated by [H-3] thymidine incorporation. A blocking experiment was performed to further address the role of CD4(+)CD25(+) T cells in ACAID. The expression of IL-10 in purified CD4(+)CD25(+) T cells was evaluated by ELISA. RESULTS: Increased frequencies of CD4(+)CD25(+) T cells, CD4(+)CD25(+) Foxp3(+) T cells and CD4(+)CD25(+) PD-1(+) T cells were observed in ACAID. The CD4(+)CD25(+) T cells from mice with ACAID showed enhanced suppressive effect on the proliferation of CD4(+)CD25(-) T cells. Treatment of BALB/c mice with anti-CD25 antibody after injection of OVA into the anterior chamber significantly inhibited the induction of ACAID. Furthermore, purified CD4(+)CD25(+) T cells from ACAID mice secreted IL-10. CONCLUSION: Our results demonstrate that Treg cells are induced in the mice undergoing ACAID. These Treg cells may play a role in the development of ACAID. 展开更多
关键词 cd4+CD25+ regulatory t cells FOXP3 ACAID IL-10 PD-1
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CD4^+CD25^(high) Regulatory Cells in Peripheral Blood of NSCLC Patients
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作者 刘莉 姚军霞 +1 位作者 丁乾 黄士昂 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2006年第5期548-551,共4页
The proportion and changes of CD4^+CD25^high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral bloo... The proportion and changes of CD4^+CD25^high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3^+, CD4^+ and CD8^+) and CD4^+CD25^high Tr cells. The results showed that the proportion of CD4^+CD25^high Tr cells in NSCLC group was significantly higher than in control group [(4.36 ±2.07) % vs (2.04±1.03) %, P〈0.01]. The proportion of CD4^+CD25^ high Tr cells in late stage was higher than that in early stage [stages Ⅰ +Ⅱ (2.264±0.6) %; stage Ⅲ(3.284± 1.38) %; stage IV (6.06 4±4.08) %] (P〈0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4^+CD25^high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4^+CD25^high Tr cells in peripheral blood may be related to im- munosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4^+CD25^high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4^+CD25^high Tr cell therapy to treat NSCLC patients may be an effective strategy. 展开更多
关键词 non-small cell lung cancer t subsets cd4^+CD25^high regulatory t cell flow cytometry survival analysis
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