Trophoblast cell line resistance to NK lysis mainly involves an HLA class I-independent mechanism.
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.
Avril
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UPRES-JE 1992 Interactions Hôte-Greffon, Laboratoire d'Immunologie, Faculté de Médecine, Tours, France.
Jarousseau
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AC
Watier
H
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Boucraut
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Le Bouteiller
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Bardos
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Thibault
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D015703:Antigens, CD / Q000276:immunology; D002460:Cell Line; D019343:Citric Acid / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000276:immunology; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D006680:HLA Antigens; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C515078:KIR2DL3 protein, human; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell; D019343:Citric Acid