Le Bouteiller Philippe, Tabiasco Julie
Inserm U563/ Université Paul Sabatier, Hôpital Purpan, Bâtiment A, BP 3028, 31024 Toulouse Cedex 3, France.
Med Sci (Paris). 2006 Aug-Sep;22(8-9):745-50. doi: 10.1051/medsci/20062289745.
The long-standing question of pregnancy immunological paradox has been generating renewed interest. Recent insights have emerged from studies in pregnant mice and humans demonstrating a number of mechanisms that prevent potentially harmful effects of maternal anti-paternal allo-antibodies (complement inhibition, partial deletion of maternal B cells specific of paternal antigens), cytotoxic CD8+ T cells (lack of HLA-A and HLA-B expression on trophoblast, local immunosuppressive molecules, transient tolerance of paternal allo-antigens specific T cells) and uterine NK cells directed against fetal-derived trophoblast cells (limited NK cytotoxic potential, trophoblast resistance to NK killing). Interestingly, it appears that not only decidual NK cell/trophoblast interactions are not harmful for the fetus but are beneficial for the placental vascularization and its subsequent development. A recent report has indeed demonstrated that during pregnancy most of the combinations of uterine KIR (killer cell immunoglobulin-like receptor) NK cell receptors and fetal HLA-C molecules expressed by trophoblast led to normal pregnancies, whereas mothers lacking activating KIR of the AA genotype when the fetus possessed HLA-C of the C2 group were at a greatly increased risk of severe preeclampsia pathology.
长期存在的妊娠免疫悖论问题引发了新的关注。最近,对怀孕小鼠和人类的研究有了新的见解,揭示了多种机制,这些机制可防止母体抗父系同种抗体(补体抑制、父系抗原特异性母体B细胞的部分缺失)、细胞毒性CD8 + T细胞(滋养层细胞上缺乏HLA - A和HLA - B表达、局部免疫抑制分子、父系同种抗原特异性T细胞的短暂耐受)以及针对胎儿来源滋养层细胞的子宫NK细胞(有限的NK细胞毒性潜能、滋养层细胞对NK杀伤的抗性)产生潜在有害影响。有趣的是,似乎不仅蜕膜NK细胞/滋养层细胞相互作用对胎儿无害,而且对胎盘血管形成及其后续发育有益。最近的一份报告确实表明,在怀孕期间,子宫KIR(杀伤细胞免疫球蛋白样受体)NK细胞受体与滋养层细胞表达的胎儿HLA - C分子的大多数组合都会导致正常妊娠,而当胎儿具有C2组HLA - C时,缺乏AA基因型激活KIR的母亲患严重先兆子痫病理的风险会大大增加。