Carosella E D
Hôpital Saint-Louis - Paris.
Bull Mem Acad R Med Belg. 2009;164(3-4):87-99; discussion 99-101.
E.D. Carosella was the pioneer who demonstrated the protective role of the HLA-G molecule on trophoblasts, which form a shield protecting the fetus from the immune reaction of its mother and subsequent reject. This non-classical HLA class I molecule is first expressed on the fertilized ovocyte, thus enabling a uterine implantation and then on the surface of the placenta trophoblast where the classical class I and II antigens are absent. He brought the first demonstration ex vivo of the protector role of HLA-G molecule present on the surface of fetal cytotrophoblast cells versus the lysis carried out by maternal decidual uterine NK cells, in both semi-allogenic combinations (maternal uterine NK cells and their own fetal cytotropohoblast counterparts) and allogenic combinations (different maternal uterine NK cells and cytotrophoblasts from different fetuses). The blockage of this protein triggers off an important cytotoxicity towards the fetal cells. Furthermore, he showed that HLA-G molecules act as an inhibitor of the T-lymphocytes, NK cells and antigen presenting cells (APC). Through his discovery Carosella also shows for the first time the three major clinical consequences: I) HLA-G molecules are crucial, as an altered expression of these molecules would lead to abortion and failed pregnancies, i.e. recurrent spontaneous abortions and preeclamptic disease. The embryo expression of soluble HLA-G molecules is a mandatory prerequisite to implantation. II) In allogenic transplantation (heart, kidney and liver-kidney graft) the expression of HLA-G protein significantly reduces acute rejection and showed an absence of chronic rejections. III) Finally, this expression on the malignant cells has a negative functional impact in the anti-tumour response. So the expression of HLA-G molecule constitutes an escape mechanism from immunosurveillance, just as the fetal cells protect themselves from the aggression of maternal immune cells.
E.D. 卡罗塞拉是一位先驱者，他证明了HLA - G分子对滋养层细胞具有保护作用，滋养层细胞形成了一个盾牌，保护胎儿免受其母亲免疫反应及随后的排斥。这种非经典的I类HLA分子首先在受精卵上表达，从而实现子宫着床，然后在胎盘滋养层表面表达，而经典的I类和II类抗原在该表面并不存在。他首次在体外证明了胎儿细胞滋养层细胞表面存在的HLA - G分子相对于母体蜕膜子宫自然杀伤细胞所进行的裂解具有保护作用，无论是在半同种异体组合（母体子宫自然杀伤细胞及其自身胎儿细胞滋养层对应物）还是同种异体组合（不同母体子宫自然杀伤细胞和来自不同胎儿的细胞滋养层）中。该蛋白质的阻断会引发对胎儿细胞的重要细胞毒性。此外，他还表明HLA - G分子可作为T淋巴细胞、自然杀伤细胞和抗原呈递细胞（APC）的抑制剂。通过他的发现，卡罗塞拉还首次展示了三个主要临床后果：I）HLA - G分子至关重要，因为这些分子表达改变会导致流产和妊娠失败，即复发性自然流产和先兆子痫疾病。可溶性HLA - G分子的胚胎表达是着床的必要先决条件。II）在同种异体移植（心脏、肾脏和肝肾联合移植）中，HLA - G蛋白的表达显著降低急性排斥反应，并显示无慢性排斥反应。III）最后，这种在恶性细胞上的表达在抗肿瘤反应中具有负面功能影响。因此，HLA - G分子的表达构成了一种免疫逃逸机制，就如同胎儿细胞保护自身免受母体免疫细胞的攻击一样。
