Laboratori d'Immunologia Cel·lular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Int Immunol. 2013 Oct;25(10):563-74. doi: 10.1093/intimm/dxt020. Epub 2013 Aug 8.
Reported alterations in T(reg) cells from type 1 diabetes (T1D) patients led us to a revision of their phenotypical features compared with controls. A fine cytometric analysis was designed for their characterization, using a panel of markers including FOXP3, CTLA4, glucocorticoid-induced TNFR family related (GITR) and CD127. The frequency of peripheral CD4(+)CD25(hi) T(reg) cells was similar between samples. However, the yield of sorted T(reg) cells was significantly lower in patients than in controls. When comparing the T(reg)-cell phenotype between samples, the only difference concerned the expression of GITR. A significant decrease of GITR(+) cells and GITR mean fluorescence intensity within the T(reg)-cell population, and to a lesser extent in the effector population, was observed in T1D compared with controls. Moreover, GITR expression was analyzed in several conditions of T-cell activation and differences were only observed in T1D T(reg) cells versus controls when responding to sub-optimal stimulation, that is, soluble anti-CD3 or medium alone but not in the presence of anti-CD3-/anti-CD28-coated beads. However, expanded T1D T(reg)-cell-mediated suppression was as efficient as that mediated by their control counterparts, showing no association between their regulatory capacity and the reduced GITR. Our results show a higher susceptibility to apoptosis in patients' versus controls' T(reg) cells, suggesting that GITR is a T(reg)-cell marker that would be primarily involved in T(reg)-cell survival rather than in their suppressor function.
报告称，1 型糖尿病（T1D）患者 T（reg）细胞的改变导致我们对其表型特征进行了重新评估，与对照相比。为了对其进行特征描述，我们设计了一个精细的细胞计量分析，使用了包括 FOXP3、CTLA4、糖皮质激素诱导的 TNFR 家族相关（GITR）和 CD127 在内的一系列标志物。外周血 CD4+CD25+hi T（reg）细胞的频率在样本之间相似。然而，患者分选的 T（reg）细胞产量明显低于对照。当比较样本之间的 T（reg）细胞表型时，唯一的区别是 GITR 的表达。与对照相比，T1D 患者中 T（reg）细胞群中的 GITR（+）细胞和 GITR 平均荧光强度显著降低，效应细胞群中的降低程度较小。此外，在 T 细胞激活的几种情况下分析了 GITR 的表达，仅在 T1D T（reg）细胞与对照相比时，在对亚最佳刺激（即可溶性抗 CD3 或单独培养基）作出反应时观察到差异，但在存在抗 CD3-/抗 CD28 包被珠时则没有观察到差异。然而，扩增的 T1D T（reg）细胞介导的抑制与对照 T（reg）细胞一样有效，表明其调节能力与降低的 GITR 之间没有关联。我们的结果表明，与对照相比，患者的 T（reg）细胞对细胞凋亡的敏感性更高，这表明 GITR 是 T（reg）细胞的标志物，主要涉及 T（reg）细胞的存活，而不是其抑制功能。
