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
目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将...目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。展开更多
Objective:The expression of programmed death 1(PD-1)on CD8^(+)T cells is associated with their activation and exhaustion,while CD57 serves as a senescence marker.The impact of PD-1^(+)and CD57^(+)CD8^(+)T cells on the...Objective:The expression of programmed death 1(PD-1)on CD8^(+)T cells is associated with their activation and exhaustion,while CD57 serves as a senescence marker.The impact of PD-1^(+)and CD57^(+)CD8^(+)T cells on the prognosis of patients with advanced high-grade serous ovarian cancer(HGSOC)remain unclear.Methods:We assessed the percentages of PD-1^(+)and CD57^(+)CD8^(+)T cells in tumor-infiltrating lymphocytes(TILs,n=85)and tumor ascites lymphocytes(TALs,n=87)using flow cytometry.The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method.Gene expression analysis elucidated the tumor immune microenvironment(TIME,n=36).Results:Patients with higher PD-1^(+)CD8^(+)TILs(>87.8%)exhibited longer platinum-free interval(PFI)and overall survival(OS).In contrast,those with elevated CD57^(+)CD8^(+)TALs(>28.69%)were more likely to experience chemotherapy and had lower complete remission rates,shorter PFI and OS.PD-1^(+)CD8^(+)TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities.Approximately 50%of CD57^(+)CD8^(+)TALs were terminally differentiated,exhibiting significantly impaired proliferation.Based on the proportions of PD-1^(+)CD8^(+)TILs and CD57^(+)CD8^(+)TALs,patients were categorized into good,median and poor prognosis groups,with median PFI of 47.78,27.29 and 11.96 months,respectively(P<0.0001).Median OS for these groups was not reach,49.23 and 30.92 months,respectively(P<0.0001).Patients with poor prognosis exhibit significantly reduced CD8^(+)T cell proportion and increased M2 macrophage in the TIME,alongside downregulation of multiple T cell activation-related pathways.Conclusions:Lower levels of PD-1^(+)CD8^(+)TILs and higher CD57^(+)CD8^(+)TALs,assessed prior to treatment,correlated with poor prognosis and suppressive TIME in advanced HGSOC.展开更多
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
基金supported by the National Natural Science Foundation of China (No.30330540)the Jiangsu Provincial Fund for Clinical Immunology Key Laboratory (No.200319)the Scientific and Technological Fund to Support Project of Suzhou City (ZS0901)
文摘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.
文摘目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。
基金supported by National Natural Science Foundation of China(No.82372888)National Key Research and Development Program of China(No.2022YFC2704000)+6 种基金National Natural Science Foundation of China(No.82273383)the Capital’s Funds for Health Improvement and Research(No.2020-2-4098)Youth program of Beijing Municipal Natural Science Foundation(No.7204328)Clinical Medicine Plus X-Young Scholars Project,Peking University(No.PKU2022LCXQ020)Key Clinical Project of Peking University Third Hospital(No.BYSY2022050)Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2021006)Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2019034).
文摘Objective:The expression of programmed death 1(PD-1)on CD8^(+)T cells is associated with their activation and exhaustion,while CD57 serves as a senescence marker.The impact of PD-1^(+)and CD57^(+)CD8^(+)T cells on the prognosis of patients with advanced high-grade serous ovarian cancer(HGSOC)remain unclear.Methods:We assessed the percentages of PD-1^(+)and CD57^(+)CD8^(+)T cells in tumor-infiltrating lymphocytes(TILs,n=85)and tumor ascites lymphocytes(TALs,n=87)using flow cytometry.The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method.Gene expression analysis elucidated the tumor immune microenvironment(TIME,n=36).Results:Patients with higher PD-1^(+)CD8^(+)TILs(>87.8%)exhibited longer platinum-free interval(PFI)and overall survival(OS).In contrast,those with elevated CD57^(+)CD8^(+)TALs(>28.69%)were more likely to experience chemotherapy and had lower complete remission rates,shorter PFI and OS.PD-1^(+)CD8^(+)TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities.Approximately 50%of CD57^(+)CD8^(+)TALs were terminally differentiated,exhibiting significantly impaired proliferation.Based on the proportions of PD-1^(+)CD8^(+)TILs and CD57^(+)CD8^(+)TALs,patients were categorized into good,median and poor prognosis groups,with median PFI of 47.78,27.29 and 11.96 months,respectively(P<0.0001).Median OS for these groups was not reach,49.23 and 30.92 months,respectively(P<0.0001).Patients with poor prognosis exhibit significantly reduced CD8^(+)T cell proportion and increased M2 macrophage in the TIME,alongside downregulation of multiple T cell activation-related pathways.Conclusions:Lower levels of PD-1^(+)CD8^(+)TILs and higher CD57^(+)CD8^(+)TALs,assessed prior to treatment,correlated with poor prognosis and suppressive TIME in advanced HGSOC.
文摘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.
