HLA class I-specific inhibitory receptors in human T lymphocytes: interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells.
A fraction of human T lymphocytes, predominantly CD8+, express receptors for HLA class I molecules typical of natural killer cells (natural killer receptors or NKRs) that inhibit T cell receptor-mediated functions. Herein, we analyzed possible mechanism(s) leading to the expression of NKRs by T cells responding to superantigens or allogeneic cells in vitro. We show that, in the presence of interleukin 15 (IL-15), T cells (depleted of NKR+ cells) responding to toxic shock syndrome toxin 1 de novo express CD94, a molecule that is part of a heterodimeric NKR with a broad specificity for different HLA class I alleles. Maximal CD94 expression occurred when IL-15 was added shortly after the cells were placed into culture, and CD94 expression started 4-6 days after addition of IL-15. Although both CD4+ and CD8+ cells expressed CD94, the simultaneous expression of NKG2A (i.e., the other component of the CD94/NKG2A inhibitory NKR) was confined to CD8+ cells. Similar data were obtained in T cell populations activated in mixed lymphocyte cultures in the presence of IL-15. The expression of CD94/NKG2A led to an impairment of allo-specific cytolytic activity by mixed lymphocyte culture-derived T cell populations or clones. Remarkably, cytolysis could be restored by the addition of anti-CD94 mAb, i.e., by masking the inhibitory NKRs.
Mingari
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MC
Dipartimento di Oncologia Clinica e Sperimentale, Università di Genova, Italy.
Ponte
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M
Bertone
S
S
Schiavetti
F
F
Vitale
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Bellomo
R
R
Moretta
A
A
Moretta
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L
D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D004768:Enterotoxins / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D011975:Receptors, Mitogen / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D013211:Staphylococcus aureus; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D001427:Bacterial Toxins; D004768:Enterotoxins; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D007519:Isoantigens; 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; D011975:Receptors, Mitogen; D055607:Receptors, Natural Killer Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal