Expression of CD94/NKG2-A on human T lymphocytes is induced by IL-12: implications for adoptive immunotherapy.
NK cell receptors (NKRs) are expressed on a subset of human T cells, predominantly CD8(+), within which they can modulate TCR-mediated functions. In an attempt to identify the mechanisms leading to NKR expression, we analyzed the capacity of IL-12 to modulate the expression by T cells of the components of the CD94/NKG2-A inhibitory receptor, a member of the C-type lectin-like family of NKR. We show that IL-12 induces the expression of NKG2-A and/or CD94 by CD8(+) T cells in culture, and that this induction was mediated neither by IFN-gamma nor by IL-15. We also show, using the redirected killing assay, that IL-12-induced expression of both CD94 and NKG2-A led to the acquisition by T cells of a functional inhibitory receptor. Expression of the CD94/NKG2-A inhibitory receptor was also induced by IL-12 during T cell Ag stimulation so that in the presence of this cytokine a high proportion of melanoma-reactive CTL induced from PBL by melanoma peptide stimulation expressed this receptor. This study emphasizes the implication of IL-12 in the modulation of immune responses through NKR induction.
Derre
Laurent
L
Institut National de la Santé et de la Recherche Médicale Unité 463, Institut de Biologie, Centre Hospitalier Régional Universitaire, 44093 Nantes Cedex 01, France.
Corvaisier
Murielle
M
Pandolfino
Marie-Christine
MC
Diez
Elisabeth
E
Jotereau
Francine
F
Gervois
Nadine
N
D015703:Antigens, CD / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009363:Neoplasm Proteins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018984:Epitopes, T-Lymphocyte; D019409:Interleukin-15; 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; D009363:Neoplasm Proteins; D010455:Peptides; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018664:Interleukin-12; D007371:Interferon-gamma