Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease.
Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease.
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DOI：
10.1016/j.clim.2008.12.006
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Nadeau KC
中科院分区：
文献类型：
--
作者：
Yu GP;Chiang D;Song SJ;Hoyte EG;Huang J;Vanishsarn C;Nadeau KC
大约 25% 的常见变异型免疫缺陷 (CVID) 受试者会患上自身免疫性疾病。我们分析了 T 细胞亚群，特别是调节性 T 细胞和 B 细胞亚群，以确定调节性 T 细胞是否存在与 CVID 受试者的自身免疫性疾病临床表型相关的变化。我们假设患有自身免疫性疾病的 CVID 受试者中调节性 T 细胞 (CD4+CD25hiCD127lo) 抑制功能会受损。在标准抑制测定中使用来自 CVID 受试者 (n=14) 和健康对照 (HC, n=5) 的纯化、分选的 Treg，我们发现患有自身免疫性疾病的 CVID 受试者 (CVID w/AI, n=8) 的 Treg 的抑制功能比没有自身免疫性疾病的 CVID 受试者 (CVID w/o AI, n=6) 和 HC (n=5) 显着减弱。通过流式细胞术通过免疫荧光抗体检测到，许多与 Treg 功能相关的蛋白质的表达下降（与没有 AI 和 HC 的 CVID 相比，Treg 中 FoxP3、Granzyme A、XCL1、pSTAT5 和 GITR 的平均荧光强度（MFI）在 CVID w/AI 中显着降低（最多 3 倍）。此外，在Treg 和 Treg 功能障碍的程度这些结果表明，Treg 功能的减弱与 CVID 受试者的自身免疫性疾病有关，并可能导致自身免疫发病机制。
Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed Tcell subsets, specifically regulatory Tcells along with B cell subsets to determine whether there were changes in regulatory T cells which would correlate with the autoimmune disease clinical phenotype in CVID subjects. We hypothesized that regulatory T cell (CD4+CD25hiCD127lo) suppressive function would be impaired in CVID subjects with autoimmune disease. Using purified, sorted Treg from CVID subjects (n=14) and from healthy controls (HC, n=5) in standard suppression assays, we found the suppressive function of Treg from CVID subjects with autoimmune disease (CVID w/ AI, n=8) to be significantly attenuated compared to CVID subjects with no autoimmune disease (CVID w/o AI, n=6) and to HC (n=5). A number of proteins associated with Treg function were decreased in expression as detected through immunofluorescent antibody via flow cytometry (mean fluorescence intensity (MFI) of FoxP3, Granzyme A, XCL1, pSTAT5, and GITR in Treg was significantly lower (by up to 3 fold) in CVID w/ AI compared to CVID w/o AI and HC. Furthermore, a statistically significant correlation was found between intracellular MFI of FoxP3, Granzyme A, and pSTAT5 in Treg and the degree of Treg dysfunction. These results suggest that attenuation of Treg function is associated with autoimmune disease in CVID subjects and may contribute to autoimmune pathogenesis.
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