GARP在CD4^+ CD25^+调节性T细胞中的表达及功能分析

Expression of GARP on CD4^+ CD25^+ cells T cells and its association with immunosuppressive activity

Foxp3+调节性T细胞对免疫反应的抑制作用主要依赖于其细胞表面的TGF-beta,GARP(glycoprotein A repetitions predominant)是一种富含亮氨酸重复序列的蛋白,与TGF-beta的激活密切相关。为探讨GARP与Foxp3+调节性T细胞的关系,本研究通过RT-PCR方法检测Foxp3+调节性T细胞GARP的mRNA水平、用流式细胞仪分析Foxp3+调节性T细胞表面GARP的表达。结果证实Foxp3+调节性T细胞在激活后其GARP分子mRNA的转录明显增加并在细胞表面表达,而效应T细胞(CD4+CD25-)在激活后没有表达。为了进一步分析GARP表达后对Foxp3+调节性T细胞抑制功能的影响,本研究在体外激活Foxp3+调节性T细胞后进行功能试验,结果发现激活的Foxp3+调节性T细胞在体外抑制效应细胞增生的能力大幅增加且不被TGF-beta的中和性抗体阻断。本研究结果提示GARP是Foxp3+调节性T细胞的特异性细胞表面分子并与其免疫调节功能密切相关。

The immunosuppressive function of Foxp3＋ regulatory T cells largely depends on the cell surface TGF-beta. GARP （glycoprotein A repetitions predominant） is a leucine rich protein that is involved in the activation of TGF-beta. In order to in- vestigate the association of GARP with Foxp3＋ regulatory T cells, we detected the GARP at mRNA and protein levels using RT-PCR and flow cytometry on CD4＋ CD25＋ cells. We found that GARP mRNA level was greatly enhanced in activated CD4＋ CD25＋ cells and we can detected GARP on the cell surface of activated regulatory T cells but not at activated CD4＋ CD25- cells. Furthermore we found the immunosuppressive function of activated CD4＋ CD25＋ was greatly enhanced in vitro suppres- sion assay and it could not be reversed through blocking TGF-beta. Our study indicates that GARP is a specific cell surface marker of Foxp3＋ regulatory T cells and associated with the immunosuppressive function of these cells.