Avril T, Jarousseau A C, Watier H, Boucraut J, Le Bouteiller P, Bardos P, Thibault G
UPRES-JE 1992 Interactions Hôte-Greffon, Laboratoire d'Immunologie, Faculté de Médecine, Tours, France.
J Immunol. 1999 May 15;162(10):5902-9.
The lack of classical HLA molecules on trophoblast prevents allorecognition by maternal T lymphocytes, but poses the problem of susceptibility to NK lysis. Expression of the nonclassical class I molecule, HLA-G, on cytotrophoblast may provide the protective effect. However, the class I-negative syncytiotrophoblast escapes NK lysis by maternal PBL. In addition, while HLA-G-expressing transfectants of LCL.721.221 cells are protected from lymphokine-activated killer lysis, extravillous cytotrophoblast cells and HLA-G-expressing choriocarcinoma cells (CC) are not. The aim of this work was therefore to clarify the role of HLA class I expression on trophoblast cell resistance to NK lysis and on their susceptibility to lymphokine-activated killer lysis. Our results showed that both JAR (HLA class I-negative) and JEG-3 (HLA-G- and HLA-Cw4-positive) cells were resistant to NK lysis by PBL and were equally lysed by IL-2-stimulated PBL isolated from a given donor. In agreement, down-regulating HLA class I expression on JEG-3 cells by acid treatment, masking these molecules or the putative HLA-G (or HLA-E) receptor CD94/NKG2 and the CD158a/p58.1 NKR with mAbs, and inducing self class I molecule expression on JAR cells did not affect NK or LAK lysis of CC. These results demonstrate that the resistance of CC to NK lysis mainly involves an HLA class I-independent mechanism(s). In addition, we show that the expression of a classical class I target molecule (HLA-B7) on JAR cells is insufficient to induce lysis by allospecific polyclonal CTL.
滋养层细胞上缺乏经典的HLA分子可防止母体T淋巴细胞进行同种异体识别，但却带来了易被NK细胞裂解的问题。细胞滋养层上非经典的I类分子HLA-G的表达可能具有保护作用。然而，I类阴性的合体滋养层细胞可逃避母体PBL的NK细胞裂解。此外，虽然LCL.721.221细胞的HLA-G表达转染体可免受淋巴因子激活的杀伤细胞裂解，但绒毛外细胞滋养层细胞和表达HLA-G的绒毛膜癌细胞（CC）却不能。因此，本研究的目的是阐明HLA I类分子表达在滋养层细胞对NK细胞裂解的抗性及其对淋巴因子激活的杀伤细胞裂解的易感性方面所起的作用。我们的结果显示，JAR细胞（HLA I类阴性）和JEG-3细胞（HLA-G和HLA-Cw4阳性）均对PBL的NK细胞裂解具有抗性，并且被从给定供体分离的IL-2刺激的PBL同等程度地裂解。同样，通过酸处理下调JEG-3细胞上的HLA I类分子表达、用单克隆抗体封闭这些分子或推定的HLA-G（或HLA-E）受体CD94/NKG2以及CD158a/p58.1 NKR，以及在JAR细胞上诱导自身I类分子表达，均不影响CC的NK或LAK裂解。这些结果表明，CC对NK细胞裂解的抗性主要涉及一种不依赖HLA I类分子的机制。此外，我们还表明，JAR细胞上经典I类靶分子（HLA-B7）的表达不足以诱导同种异体特异性多克隆CTL的裂解。
