CD4+CD25+ immunoregulatory T cells:: Gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor

CD4+CD25+ immunoregulatory T cells:: Gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor
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DOI:
10.1016/s1074-7613(02)00280-7
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发表时间:
2002-02-01
期刊:
影响因子:
32.4
通讯作者:
Byrne, MC
Byrne, MC
中科院分区:
医学1区
文献类型:
--
作者:
McHugh, RS;Whitters, MJ;Byrne, MC

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CD4(+)CD25(+)免疫调节性T细胞是一种独特的胸腺来源细胞,在体外和体内都能有效抑制效应性T细胞的功能。我们用DNA芯片分析了CD4(+)CD25(+)和CD4(+)CD25(-)T细胞,鉴定了29个在静止亚群中差异表达的基因,以及77个在激活后差异表达的基因。这些基因中的大多数在CD4(+)CD25(+)人群中升高,表明以前激活的表型。其中包括一些拮抗信号的基因,包括SOCS家族的成员,这可能有助于它们的无能表型。多种细胞表面受体在CD4(+)CD25(+)细胞中的表达也增加,包括肿瘤坏死因子受体超家族成员GITR。重要的是,GITR的抗体取消了抑制,证明了这种受体在调节CD4(+)CD25(+)T细胞亚群中的功能作用。
CD4(+)CD25(+) immunoregulatory T cells represent a unique lineage of thymic-derived cells that potently suppress both in vitro and in vivo effector T cell function. We analyzed CD4(+)CD25(+) and CD4(+)CD25(-) T cells by DNA microarray, identifying 29 genes differentially expressed in the resting subpopulations, and 77 that were differentially expressed following activation. Most of these genes were elevated in the CD4(+)CD25(+) population, suggesting a previously activated phenotype. Among these were a number of genes that antagonize signaling, including members of the SOCS family, which may contribute to their anergic phenotype. Multiple cell surface receptors also had increased expression in CD4(+)CD25(+) cells, including GITR, a member of the TNF receptor superfamily. Importantly, antibodies to GITR abrogated suppression, demonstrating a functional role for this receptor in regulating the CD4(+)CD25(+) T cell subset.