Department of Medical Biology and Central Electron Microscope Laboratory, Medical School, Pecs University, Pecs, Hungary.
János Szentágothai Research Centre, Pecs University, Pecs, Hungary.
Med Princ Pract. 2018;27(4):301-307. doi: 10.1159/000491576. Epub 2018 Jun 27.
This review aims to provide a brief historical overview of the feto-maternal immunological relationship, which profoundly influences the outcome of pregnancy. The initial question posed in the 1950s by Medawar [Symp Soc Exp Biol. 1953; 7: 320-338] was based on the assumption that the maternal immune system recognizes the fetus as an allograft. Indeed, based on the association between HLA-matching and spontaneous miscarriage, it became obvious that immunological recognition of pregnancy is required for a successful gestation. The restricted expression of polymorphic HLA antigens on the trophoblast, together with the presence of nonpolymorphic MHC products, excludes recognition by both T and NK cells of trophoblast-presented antigens; however, γδ T cells, which constitute the majority of decidual T cells, are likely candidates. Indeed, a high number of activated, progesterone receptor-expressing γδ T cells are present in the peripheral blood of healthy pregnant women and, in the presence of progesterone, these cells secrete an immunomodulatory protein called progesterone-induced blocking factor (PIBF). As early as in the peri-implantation period, the embryo communicates with the maternal immune system via PIBF containing extracellular vesicles. PIBF contributes to the dominance of Th2-type reactivity which characterizes normal pregnancy by inducing increased production of Th2 cytokines. The high expression of this molecule in the decidua might be one of the reasons for the low cytotoxic activity of decidual NK cells.
本文旨在简要回顾母体-胎儿免疫关系的历史，该关系对妊娠结局有深远影响。Medawar 于 20 世纪 50 年代提出的最初问题[Symp Soc Exp Biol. 1953; 7: 320-338]基于这样一种假设，即母体免疫系统将胎儿视为同种异体移植物。事实上，基于 HLA 匹配与自然流产之间的关联，免疫识别妊娠显然是成功妊娠所必需的。滋养层上有限表达的多态性 HLA 抗原，加上非多态性 MHC 产物的存在，排除了 T 和 NK 细胞对滋养层呈现抗原的识别；然而，构成大部分蜕膜 T 细胞的 γδ T 细胞可能是候选细胞。事实上，健康孕妇外周血中有大量活化的、孕激素受体表达的 γδ T 细胞，在孕激素存在的情况下，这些细胞会分泌一种称为孕激素诱导阻断因子（PIBF）的免疫调节蛋白。早在着床期，胚胎就通过含有外泌体的 PIBF 与母体免疫系统进行交流。PIBF 通过诱导 Th2 细胞因子产生增加，有助于维持正常妊娠的 Th2 型反应优势。这种分子在蜕膜中的高表达可能是蜕膜 NK 细胞细胞毒性活性低的原因之一。
