APC dysfunction is correlated with defective suppression of T cell proliferation in human type 1 diabetes.
APC dysfunction is correlated with defective suppression of T cell proliferation in human type 1 diabetes.
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DOI：
10.1016/j.clim.2008.10.005
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
She JX
中科院分区：
文献类型：
--
作者：
Jin Y;Chen X;Podolsky R;Hopkins D;Makala LH;Muir A;She JX
人们普遍认为CD4+CD25+调节性T细胞（Treg）在1型糖尿病（T1D）和其他自身免疫性疾病中存在缺陷。然而，这一结论是基于少数受试者的次优体外抑制结果。此外，负责次优抑制的细胞尚未定义。因此，我们使用来自T1D患者和正常对照的自体和异体供体treg、效应T细胞和抗原呈递细胞（APC）进行了广泛的体外抑制实验。我们的体外抑制数据显示，与对照组（6.3%）相比，自体Treg“极低抑制”活性（定义为< 25%）的T1D患者比例（40.0%）显著高于对照组（p=0.002）。已发表结果的荟萃分析证实了这一观察结果，T1D患者中有45.7%的低抑制因子，对照组中有7.8% （p = 0.00002）。有趣的是，利用异种Tregs、效应T细胞和APC进行的抑制实验表明，APC的来源与抑制活性相关。正常对照中CD4+CD25+和CD4+CD25hi T细胞的频率随年龄增加，而T1D患者中CD4+CD25+和CD4+CD25hi T细胞的频率随年龄增加而增加，导致年轻T1D患者CD4+CD25+和CD4+CD25hi (p = 0.009) T细胞的频率明显高于年龄匹配的对照组，而老年T1D患者CD4+CD25+和CD4+CD25hi T细胞的频率略低于年龄匹配的对照组（p = 0.003）和CD4+CD25hi （p = 0.08）。
It is widely believed that CD4+CD25+ regulatory T cells (Treg) are defective in type 1 diabetes (T1D) and other autoimmune diseases. However, this conclusion is based on the suboptimal in vitro suppression results from very small numbers of subjects. Furthermore, the cells responsible for the suboptimal suppression have not been defined. Therefore, we carried out extensive in vitro suppression assays using both autologous and heterologous donors of Tregs, effector T cells and antigen-presenting cells (APC) from both T1D patients and normal controls. Our in vitro suppression data indicated that a significantly higher proportion (40.0%) of T1D patients have “very low suppression” activity (defined as < 25%) by autologous Treg compared to controls (6.3%) (p=0.002). Meta-analysis of the published results confirmed this observation with 45.7% low suppressors in T1D and 7.8% in controls (p = 0.00002). Interestingly, suppression assays using heterologous Tregs, effector T cells and APC suggest that the source of APC is correlated with the suppression activity. The frequencies of CD4+CD25+ and CD4+CD25hi T cells were found to increase with age in normal controls but not in T1D patients, resulting in significantly higher frequencies of CD4+CD25+ (p = 0.001) and CD4+CD25hi (p = 0.009) T cells in young T1D subjects than age-matched controls but slightly lower CD4+CD25+ (p = 0.003) and CD4+CD25hi (p = 0.08) T cells in old T1D subjects than age-matched controls.
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DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.7
作者：
Alard, Pascale;Manirarora, Jean N.;Kosiewicz, Michele M.
通讯作者：
Kosiewicz, Michele M.
影响因子：
4.4
作者：
Baecher-Allan, C;Viglietta, V;Hafler, DA
通讯作者：
Hafler, DA
影响因子：
7.7
作者：
Brusko, TM;Wasserfall, CH;Atkinson, MA
通讯作者：
Atkinson, MA