Han Guang Ming, O'Neil-Andersen Nancy J, Zurier Robert B, Lawrence David A
Biggs Laboratory, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-0509, USA.
Cell Immunol. 2008 May-Jun;253(1-2):92-101. doi: 10.1016/j.cellimm.2008.05.007. Epub 2008 Jul 22.
Accumulating evidences support that CD4(+)CD25(high) T regulatory (Treg) cells play an essential role in controlling and preventing autoimmunity. Paradoxically, RA patients have elevated numbers of circulating CD4(+)CD25(high) T cells, however, the inflammation is still ongoing. Further identification of these CD4(+)CD25(high) T cells may contribute to a better understanding of underlying mechanisms. We show here that these CD4(+)CD25(high) T cells were composed of CD4(+)CD25(high)FoxP3(+) Treg cells and activated CD4(+)CD25(high)FoxP3(-) effector cells. Moreover, there were significantly more Treg cells and effector T cells expressing GITR, and more monocytes expressing GITR-L. Thus, although RA patients have elevated numbers of CD4(+)CD25(high) T cells, the suppressive function is not increased, because of the increased number of activated effector T cells. In addition, the GITR-GITR-L system was activated in RA patients, which might lead to diminish suppressive activity of Treg cells and/or lead to resistance of activated effector T cells to suppression by Treg cells, thus, contributing to the ongoing inflammation in RA patients.
越来越多的证据支持CD4(+)CD25(高)调节性T(Treg)细胞在控制和预防自身免疫中起重要作用。矛盾的是，类风湿关节炎(RA)患者循环中CD4(+)CD25(高)T细胞数量增加，然而炎症仍在持续。对这些CD4(+)CD25(高)T细胞的进一步鉴定可能有助于更好地理解其潜在机制。我们在此表明，这些CD4(+)CD25(高)T细胞由CD4(+)CD25(高)FoxP3(+)Treg细胞和活化的CD4(+)CD25(高)FoxP3(-)效应细胞组成。此外，表达糖皮质激素诱导肿瘤坏死因子受体(GITR)的Treg细胞和效应T细胞明显更多，表达GITR配体(GITR-L)的单核细胞也更多。因此，尽管RA患者CD4(+)CD25(高)T细胞数量增加，但由于活化效应T细胞数量增加，其抑制功能并未增强。此外，RA患者中GITR-GITR-L系统被激活，这可能导致Treg细胞抑制活性降低和/或导致活化效应T细胞对Treg细胞抑制产生抵抗，从而导致RA患者炎症持续。
