Control of self-reactive cytotoxic T lymphocytes expressing gamma delta T cell receptors by natural killer inhibitory receptors

• Published in: European journal of immunology Vol. 27; no. 11; p. 2812
• Main Authors: Halary, F, Peyrat, M A, Champagne, E, Lopez-Botet, M, Moretta, A, Moretta, L, Vié, H, Fournié, J J, Bonneville, M
• Format: Journal Article
• Language: English
• Published: Germany 01.11.1997
• Subjects: Adult; Burkitt Lymphoma; Clone Cells; Cytotoxicity, Immunologic - drug effects; Histocompatibility Antigens Class I - physiology; HLA Antigens - physiology; Humans; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Leukemia, Erythroblastic, Acute; Lymphocyte Activation - drug effects; Lymphocyte Count; Multiple Myeloma; Receptors, Antigen, T-Cell, gamma-delta - biosynthesis; Receptors, Antigen, T-Cell, gamma-delta - physiology; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - immunology; Receptors, Immunologic - physiology; Receptors, KIR; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Tumor Cells, Cultured
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830271111

The majority of peripheral blood gamma delta T cells in human adults expresses T cell receptors (TCR) with identical V regions (V gamma 9 and V delta 2). These V gamma 9 V delta 2 T cells recognize the major histocompatibility complex (MHC) class I-deficient B cell line Daudi and broadly distributed nonpeptidic antigens present in bacteria and parasites. Here we show that unlike alpha beta or V gamma 9- gamma delta T cells, the majority of V gamma 9V delta 2 T cells harbor natural killer inhibitory receptors (KIR) (mainly CD94/NKG2A heterodimers), which are known to deliver inhibitory signals upon interaction with MHC class I molecules. Within V gamma 9V delta 2 T cells, KIR were mainly expressed by clones exhibiting a strong lytic activity against Daudi cells. In stark contrast, almost all V gamma 9V delta 2 T cell clones devoid of killing activity were KIR-, thus suggesting a coordinate acquisition of KIR and cytotoxic activity within V gamma 9V delta 2 T cells. In functional terms, KIR inhibited lysis of MHC class I-positive tumor B cell lines by V gamma 9V delta 2 cytotoxic T lymphocytes (CTL) and raised their threshold of activation by microbial antigens presented by MHC class I-positive cells. Furthermore, masking KIR or MHC class I molecules revealed a TCR-dependent recognition by V gamma 9V delta 2 CTL of ligands expressed by activated T lymphocytes, including the effector cells themselves. Taken together, these results suggest a general implication of V gamma 9V delta 2 T cells in immune response regulation and a central role of KIR in the control of self-reactive gamma delta CTL.