Regulation of major histocompatibility complex class II gene expression in trophoblast cells.
Regulation of major histocompatibility complex class II gene expression in trophoblast cells.
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DOI：
10.1186/1477-7827-2-52
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发表时间：
2004-07-05
期刊：
影响因子：
--
通讯作者：
Holtz R
中科院分区：
文献类型：
--
作者：
Murphy SP;Choi JC;Holtz R
滋养层细胞是独特的，因为它们是组成型或暴露于IFN-γ后不表达主要组织相容性复合体（MHC）II类抗原的少数哺乳动物细胞类型之一。 滋养层细胞上MHC II类抗原表达的缺乏被假定为半同种异体胎儿逃避母体免疫系统的免疫排斥反应的基本机制之一。 与这一假设一致，来自患有病因不明的慢性炎症和自发性复发性流产的妇女的胎盘的滋养层细胞已被报道异常表达MHC II类抗原。 滋养层细胞上MHC II类抗原表达的缺乏是由于II类反式激活因子（CIITA）的表达沉默，所述II类反式激活因子是组成型和IFN-γ诱导型MHC II类基因转录所必需的反式作用因子。 用CIITA表达载体转染滋养层细胞激活MHC II类和Ia类抗原表达，这赋予滋养层细胞激活辅助T细胞的能力和对细胞毒性T淋巴细胞裂解的敏感性。 总的来说，这些研究强烈表明，严格沉默滋养层细胞中的CIITA（因此MHC II类）基因表达对于预防母体免疫系统对胎儿的免疫排斥反应至关重要。 这篇综述的重点是总结研究新的机制，其中CIITA是沉默的滋养层细胞。 阐明滋养层细胞中CIITA的沉默可能有助于了解半同种异体胎儿在妊娠期间如何逃避母体免疫系统的免疫排斥。
Trophoblast cells are unique because they are one of the few mammalian cell types that do not express major histocompatibility complex (MHC) class II antigens, either constitutively or after exposure to IFN-γ. The absence of MHC class II antigen expression on trophoblast cells has been postulated to be one of the essential mechanisms by which the semi-allogeneic fetus evades immune rejection reactions by the maternal immune system. Consistent with this hypothesis, trophoblast cells from the placentas of women suffering from chronic inflammation of unknown etiology and spontaneous recurrent miscarriages have been reported to aberrantly express MHC class II antigens. The lack of MHC class II antigen expression on trophoblast cells is due to silencing of expression of the class II transactivator (CIITA), a transacting factor that is essential for constitutive and IFN-γ-inducible MHC class II gene transcription. Transfection of trophoblast cells with CIITA expression vectors activates both MHC class II and class Ia antigen expression, which confers on trophoblast cells both the ability to activate helper T cells, and sensitivity to lysis by cytotoxic T lymphocytes. Collectively, these studies strongly suggest that stringent silencing of CIITA (and therefore MHC class II) gene expression in trophoblast cells is critical for the prevention of immune rejection responses against the fetus by the maternal immune system. The focus of this review is to summarize studies examining the novel mechanisms by which CIITA is silenced in trophoblast cells. The elucidation of the silencing of CIITA in trophoblast cells may shed light on how the semi-allogeneic fetus evades immune rejection by the maternal immune system during pregnancy.