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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-02, Vol.95 (3), p.1172-1177
• Main Authors: Mingari, Maria Cristina, Ponte, Marco, Bertone, Stefania, Schiavetti, Francesca, Vitale, Chiara, Bellomo, Rosa, Moretta, Alessandro, Moretta, Lorenzo
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Antigens, CD - immunology; Bacterial Toxins; Biological Sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cells; Clone Cells; Cultured cells; Cytokines; Enterotoxins - pharmacology; Fluorescence; Histocompatibility Antigens Class I - metabolism; HLA antigens; Humans; Immune system; Immunology; Interleukin-15 - pharmacology; Isoantigens - immunology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Lectins, C-Type; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; Lymphocytes; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - immunology; Mixed lymphocyte culture test; Molecules; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily C; NK Cell Lectin-Like Receptor Subfamily D; Receptors; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - immunology; Receptors, Mitogen - biosynthesis; Receptors, Mitogen - immunology; Receptors, Mitogen - metabolism; Receptors, Natural Killer Cell; Staphylococcus aureus; Superantigens - immunology; T lymphocytes; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.3.1172

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.