Frisullo Giovanni, Nociti Viviana, Iorio Raffaele, Patanella Agata K, Caggiula Marcella, Marti Alessandro, Sancricca Cristina, Angelucci Francesco, Mirabella Massimiliano, Tonali Pietro A, Batocchi Anna P
Department of Neuroscience, Institute of Neurology, Catholic University, Rome.
Immunology. 2009 Jul;127(3):418-28. doi: 10.1111/j.1365-2567.2008.02963.x. Epub 2008 Nov 7.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system and a defect in the regulatory T-cell subset seems to be involved in the pathogenesis of the disease. Foxp3 is a transcription factor that is selectively expressed in CD4+ CD25+ regulatory T cells and is required for their development and function. T-bet is a key transcription factor for the development of T helper 1 (Th1) cells. We found that both the percentage of circulating CD4+ CD25+ Foxp3+ cells and Foxp3 expression were lower in relapsing-remitting (RR) MS patients during relapses than during remission. Otherwise, the percentage of CD4+ T-bet+ T cells and T-bet expression in CD4+ T cells were higher in relapsing than in remitting RRMS patients. CD4+ CD25+ T cells both from relapsing and from remitting RRMS patients showed significantly less capacity than corresponding cells from healthy subjects to suppress autologous CD4+ CD25(-) T-cell proliferation, despite a similar Foxp3 expression level. CD4+ CD25+ T cells from healthy subjects and patients in remission clearly reduced T-bet mean fluorescence intensity (MFI) in CD4+ CD25(-) T cells up to a ratio of 1:10, whereas CD4+ CD25+ T cells from patients in relapse were able to reduce T-bet expression only at a high ratio. Our data indicate that the increased number of regulatory T (T-reg) cells and the increased Foxp3 expression in circulating CD4+ CD25+ T cells may contribute to the maintenance of tolerance in the remission phase of MS. Moreover, the inhibitory capacity of CD4+ CD25+ T cells seems to be impaired in relapsing patients under inflammatory conditions, as shown by the high levels of T-bet expression in CD4+ T cells.
多发性硬化症（MS）是一种中枢神经系统的慢性炎性脱髓鞘疾病，调节性T细胞亚群的缺陷似乎参与了该疾病的发病机制。Foxp3是一种转录因子，在CD4+ CD25+调节性T细胞中选择性表达，是其发育和功能所必需的。T-bet是辅助性T细胞1（Th1）细胞发育的关键转录因子。我们发现，复发缓解型（RR）MS患者复发期循环CD4+ CD25+ Foxp3+细胞的百分比和Foxp3表达均低于缓解期。此外，复发期RRMS患者CD4+ T-bet+ T细胞的百分比和CD4+ T细胞中T-bet的表达高于缓解期。来自复发期和缓解期RRMS患者的CD4+ CD25+ T细胞，尽管Foxp3表达水平相似，但与健康受试者相应细胞相比，抑制自体CD4+ CD25（-）T细胞增殖的能力明显较低。健康受试者和缓解期患者的CD4+ CD25+ T细胞在高达1:10的比例下能明显降低CD4+ CD25（-）T细胞中的T-bet平均荧光强度（MFI），而复发期患者的CD4+ CD25+ T细胞仅在高比例时才能降低T-bet表达。我们的数据表明，调节性T（T-reg）细胞数量增加以及循环CD4+ CD25+ T细胞中Foxp3表达增加可能有助于MS缓解期耐受性的维持。此外，如CD4+ T细胞中T-bet表达水平高所示，复发期患者在炎症条件下CD4+ CD25+ T细胞的抑制能力似乎受损。
