CD4+CD25lowGITR+ cells: A novel human CD4+ T-cell population with regulatory activity
CD4+CD25lowGITR+ cells: A novel human CD4+ T-cell population with regulatory activity
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DOI：
10.1002/eji.201040943
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发表时间：
2011-08-01
影响因子：
5.4
通讯作者：
Riccardi, Carlo
中科院分区：
文献类型：
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作者：
Bianchini, Rodolfo;Bistoni, Onelia;Riccardi, Carlo
Treg亚群在维持外周耐受性中起作用，其特征在于标记物如叉头翼螺旋转录因子（FOXP 3）和⑶ 25，并产生抑制性细胞因子，如IL-10和TGF-β。糖皮质激素诱导的TNF受体家族相关（GITR）蛋白已被认为调节小鼠中的Treg活性。本研究的目的是探讨GITR在人CD 4（+）T淋巴细胞中的表达及其在Treg功能中的可能作用。结果表明，外周血中的CD 4（+）T细胞亚群表达GITR和低水平的CD 25（CD 4（+）CD 25（低）GITR（+））。这些细胞显示Treg特征，因为它们表达F0 XP 3、IL-10、TGF-β并且是无反应性的，但是与天然的T细胞相反，表达低水平的CTLA-4并且是⑶ 127（高）。CD 4（+）CD 25（低）GITR（+）细胞占CD 4（+）T细胞群的百分比较低（0.32-1.74%），主要是记忆细胞。功能实验表明，CD 4（+）CD 25（低）GITR（+）细胞具有依赖于TGF-β的相关抑制活性。此外，抗GITR Ab抑制其抑制活性，如在CD 4（+）CD 25（+）鼠TCFs中观察到的。总之，这些数据表明人CD 4（+）CD 25（低）GITR（+）细胞代表了不同的Treg亚群。
Treg subsets play a role in sustaining peripheral tolerance, are characterized by markers such as forkhead winged-helix transcription factor (FOXP3) and CD25, and produce suppressive cytokines, such as IL-10 and TGF-beta. Glucocorticoid-induced TNF receptor family-related (GITR) protein has been suggested to regulate Treg activity in mice. The aim of our study was to investigate GITR expression in human CD4(+) T lymphocytes and its possible role in Treg function. Results indicate that a subset of CD4(+) T cells in the peripheral blood expresses GITR and low levels of CD25 (CD4(+)CD25(low)GITR(+)). These cells show Treg features as they express FOXP3, IL-10, TGF-beta and are anergic but, as opposed to natural Tregs, express low levels of CTLA-4 and are CD127(high). CD4(+)CD25(low)GITR(+) cells represent a low percentage of the CD4(+) T-cell population (0.32-1.74%) and are mostly memory cells. Functional experiments demonstrated that CD4(+)CD25(low)GITR(+) cells have relevant suppressive activity that depends on TGF-beta. Moreover, an anti-GITR Ab inhibited their suppressive activity, as observed in CD4(+) CD25(+) murine Tregs. Taken together, these data indicate that human CD4(+)CD25(low)GITR(+) cells represent a distinct Treg subpopulation.