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 CD4^+CD25^+调节性 T 细胞、共刺激通路阻断剂 CD154单抗及两者联合应用在抑制大鼠肝移植急性排斥反应中的作用。方法 48例原位肝移植大鼠(DA→Lewis)分为 A 组:对照组;B 组:术前7 d 回输经 DA 大鼠脾细胞体外激活的 Lewis 大...目的探讨 CD4^+CD25^+调节性 T 细胞、共刺激通路阻断剂 CD154单抗及两者联合应用在抑制大鼠肝移植急性排斥反应中的作用。方法 48例原位肝移植大鼠(DA→Lewis)分为 A 组:对照组;B 组:术前7 d 回输经 DA 大鼠脾细胞体外激活的 Lewis 大鼠 CD4^+CD25^+细胞;C 组:术后第1、2 d 腹腔注射 CD154单抗(15 mg/kg);D 组:联合应用 CD4^+CD25^+细胞和 CD154单抗。术后7 d 各组处死6只受体,观察移植肝病理变化,检测移植肝内 T 细胞亚群和细胞因子白细胞介素-2(IL-2)、IL-4、IL-10和转化生长因子β1(TGFβ1)表达情况;分离脾淋巴细胞与供体行单向混合淋巴细胞反应观察刺激指数。余大鼠观察生存情况。结果 D 组平均存活时间(52.00±10.64)d 明显长于其他各组(P<0.01);移植肝内淋巴细胞浸润数量(2.47±0.61)×10~6和 CD8^+细胞百分比(14.2±3.0)%明显低于 B、C 组(P<0.05、P<0.01),而 CD4^+CD25^+细胞比例(16.4±4.3)%高于 B、C 组(P<0.05,P<0.01)。移植物内 IL-2 mRNA 表达 A 组最高,D 组最弱;IL-4 mRNA 各组均弱表达;IL-10mRNAB、D 组高表达,A、C 组未表达;TGFβ1 mRNA B、D 组表达明显强于 A、C 组。单向混合淋巴细胞反应 D 组刺激指数最低(P<0.05)。结论 CD4^+CD25^+调节性 T 细胞和共刺激通路阻断剂 CD154单抗均能抑制大鼠肝移植急性排斥反应;联合应用 CD154单抗明显增强 CD4^+CD25^+调节性 T 细胞对急性排斥反应的抑制作用。展开更多
文摘本研究探讨人骨髓间充质干细胞(human mesenchymalstem cells,hMSC)对同种异体CD4+CD25+调节T细胞的作用,进一步查明人骨髓间充质干细胞对T淋巴细胞免疫调节作用的可能机制。从人骨髓中分离培养hMSC,通过免疫组织化学方法检测其表面标记并进行鉴定。从非亲缘供者健康人外周血中提取单个核细胞,在IL-2作用下体外培养,实验组加入不同数量级hMSC(1×103,1×104,1×105)共培养5天,对照组加入PBS。于结束培养前18小时经3H-TdR标记后用β液体闪烁计数仪检测T淋巴细胞增殖,流式细胞术检测各组CD4+CD25+T细胞的百分率,RT-PCR检测各组细胞Foxp3的相对表达量(Foxp3/β-actin),ELISA分别测定上清中TGF-β、IL-10、IFN-γ和IL-12的表达。Pearson检验分析Foxp3相对表达量与CD4+CD25+T细胞百分率的相关性,以及Foxp3相对表达量、CD4+CD25+T细胞百分率与T淋巴细胞增殖程度(counts per minute,CPM值),细胞因子TGF-β、IL-10、IFN-γ和IL-12表达量的相关性。结果表明:hMSC能明显抑制T淋巴细胞增殖,且抑制作用与hMSC呈剂量依赖性;实验组各组CD4+CD25+T细胞亚群含量以及Foxp3相对表达水平均较对照组明显增加(p<0.05),且实验组间比较差异仍具有统计学意义(p<0.05);Foxp3表达水平、CD4+CD25+T细胞百分率与T淋巴细胞增殖水平呈明显负相关(p<0.05),与TGF-β、IL-10表达量呈明显正相关,而与IFN-γ和IL-12的表达无明显相关性。结论:hMSC呈剂量依赖性抑制同种异体淋巴细胞增殖,其机制可能与hMSC通过分泌TGF-β、IL-10促进CD4+CD25-T细胞向表达Foxp3的CD4+CD25+调节T细胞转化,进而发挥免疫抑制作用有关。
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 CD4^+CD25^+调节性 T 细胞、共刺激通路阻断剂 CD154单抗及两者联合应用在抑制大鼠肝移植急性排斥反应中的作用。方法 48例原位肝移植大鼠(DA→Lewis)分为 A 组:对照组;B 组:术前7 d 回输经 DA 大鼠脾细胞体外激活的 Lewis 大鼠 CD4^+CD25^+细胞;C 组:术后第1、2 d 腹腔注射 CD154单抗(15 mg/kg);D 组:联合应用 CD4^+CD25^+细胞和 CD154单抗。术后7 d 各组处死6只受体,观察移植肝病理变化,检测移植肝内 T 细胞亚群和细胞因子白细胞介素-2(IL-2)、IL-4、IL-10和转化生长因子β1(TGFβ1)表达情况;分离脾淋巴细胞与供体行单向混合淋巴细胞反应观察刺激指数。余大鼠观察生存情况。结果 D 组平均存活时间(52.00±10.64)d 明显长于其他各组(P<0.01);移植肝内淋巴细胞浸润数量(2.47±0.61)×10~6和 CD8^+细胞百分比(14.2±3.0)%明显低于 B、C 组(P<0.05、P<0.01),而 CD4^+CD25^+细胞比例(16.4±4.3)%高于 B、C 组(P<0.05,P<0.01)。移植物内 IL-2 mRNA 表达 A 组最高,D 组最弱;IL-4 mRNA 各组均弱表达;IL-10mRNAB、D 组高表达,A、C 组未表达;TGFβ1 mRNA B、D 组表达明显强于 A、C 组。单向混合淋巴细胞反应 D 组刺激指数最低(P<0.05)。结论 CD4^+CD25^+调节性 T 细胞和共刺激通路阻断剂 CD154单抗均能抑制大鼠肝移植急性排斥反应;联合应用 CD154单抗明显增强 CD4^+CD25^+调节性 T 细胞对急性排斥反应的抑制作用。
