Shao Ling, Jacobs Adam R, Johnson Valrie V, Mayer Lloyd
Immunobiology Center and Department of Obstetrics and Gynecology, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Immunol. 2005 Jun 15;174(12):7539-47. doi: 10.4049/jimmunol.174.12.7539.
The immunological basis by which a mother tolerates her semi-allogeneic fetus remains poorly understood. Several mechanisms are likely to contribute to this phenomenon including active immune regulation by regulatory T cells. In this article, we report that human placental trophoblasts activate a clonal population of CD8(+) T cells with regulatory function. These cells are not MHC class I restricted, but require costimulation through a member of the carcinoembryonic Ag family present on early gestation trophoblasts. These regulatory T cells express the mucosal markers CD101 and CD103 and display selective usage of the TCR gene Vbeta9. CD8(+) T cells isolated from the peripheral blood of pregnant mothers (16-28 wk) also demonstrate expansions in the same Vbeta family (Vbeta9), signaling a possible role for these cells in preventing fetal rejection in vivo. We have previously characterized a subset of CD8(+) regulatory T cells activated by the combination of the nonclassical class I molecule CD1d and a costimulatory molecule of the carcinoembryonic Ag family present on the intestinal epithelium. These data support the concept that distinct regulatory T cell populations exist at different sites and may be regulated locally by unique restriction elements, costimulatory signals, and Ags.
母亲如何耐受其半同种异体胎儿的免疫基础仍知之甚少。几种机制可能导致了这一现象,包括调节性T细胞的主动免疫调节。在本文中,我们报告人胎盘滋养层细胞激活了一群具有调节功能的CD8(+) T细胞克隆。这些细胞不受MHC I类分子限制,但需要通过早孕滋养层细胞上存在的癌胚抗原家族成员进行共刺激。这些调节性T细胞表达黏膜标志物CD101和CD103,并显示出TCR基因Vβ9的选择性使用。从怀孕母亲(16 - 28周)外周血中分离出的CD8(+) T细胞在同一Vβ家族(Vβ9)中也有扩增,表明这些细胞在体内预防胎儿排斥反应中可能发挥作用。我们之前已经鉴定了一类由非经典I类分子CD1d和存在于肠上皮的癌胚抗原家族共刺激分子共同激活的CD8(+)调节性T细胞亚群。这些数据支持这样一种概念,即不同的调节性T细胞群体存在于不同部位,并且可能由独特的限制元件、共刺激信号和抗原进行局部调节。