Hunt Joan S, Petroff Margaret G, McIntire Ramsey H, Ober Carole
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160-7400, USA.
FASEB J. 2005 May;19(7):681-93. doi: 10.1096/fj.04-2078rev.
Multiple mechanisms underlie the surprising willingness of mothers to tolerate genetically different fetal tissues during pregnancy. Chief among these is the choice of HLA-G, a gene with few alleles, rather than the highly polymorphic HLA-A and -B genes, for expression by the placental cells that interface directly with maternal blood and tissues. Novel aspects of this major histocompatibility complex class Ib gene include alternative splicing to permit production of membrane and soluble isoforms, deletions that dampen responses to interferons, and a shortened cytoplasmic tail that affects expression at the cell surface. Placental cells migrating into the maternal uterus synthesize both membrane and soluble isoforms, which interact with inhibitory receptors on leukocytes such as ILT2 and ILT4. Cytotoxic T lymphocytes either die or reduce production of one of their major coreceptor/activator cell surface molecules, CD8; natural killer cells are immobilized and mononuclear phagocytes are programmed into suppressive modes characterized by high production of anti-inflammatory cytokines. The idea that placental HLA-G proteins facilitate semiallogeneic pregnancy by inhibiting maternal immune responses to foreign (paternal) antigens via these actions on immune cells is now well established, and the postulate that the recombinant counterparts of these proteins may be used as powerful tools for preventing immune rejection of transplanted organs is gaining in popularity.
母亲在孕期能够容忍基因不同的胎儿组织，这种令人惊讶的现象背后存在多种机制。其中最主要的是胎盘细胞（直接与母体血液和组织接触）选择表达HLA - G基因，该基因等位基因较少，而非高度多态的HLA - A和 - B基因。这种主要组织相容性复合体Ib类基因的新特性包括可变剪接以产生膜结合型和可溶性异构体、可减弱对干扰素反应的缺失以及影响细胞表面表达的缩短的胞质尾。迁移至母体子宫的胎盘细胞会合成膜结合型和可溶性异构体，它们与白细胞上的抑制性受体如ILT2和ILT4相互作用。细胞毒性T淋巴细胞要么死亡，要么减少其主要共受体/激活细胞表面分子之一CD8的产生；自然杀伤细胞被固定，单核吞噬细胞被编程进入以大量产生抗炎细胞因子为特征的抑制模式。胎盘HLA - G蛋白通过对免疫细胞的这些作用抑制母体对异体（父源）抗原的免疫反应，从而促进半同种异体妊娠，这一观点现已得到充分证实，并且这些蛋白的重组对应物可能用作预防移植器官免疫排斥的有力工具这一假设也越来越受到关注。
