title: Cyclosporin A regulates human NK cell apoptosis induced by soluble HLA-I or by target cells.
abstract: Human natural killer (NK) cells are effectors of innate immunity, capable of killing transformed or virus-infected cells and producing pro-inflammatory cytokines. Soluble molecules of HLA-I (sHLA-I), which are significantly increased in the serum of patients affected by auto-immune or infectious or neoplastic diseases, induce NK cell apoptosis interacting with its ligands, such as CD8 or the activating isoforms of members of inhibitory superfamily receptors (IRS). This cell death is accompanied by the release of large amounts of interferon-gamma. NK cells can kill autologous target cells, including antigen presenting cells or infected or tumor cells, by engaging the natural cytotoxicity receptors (NCR) NKp30, or NKp44 and NKp46. Again, the binding between NCR on NK cells and their putative ligands on targets leads to NK cell apoptosis. FasL produced and secreted by NK cells is responsible for the NK cell apoptosis induced by either HLA-I receptors or NCR. Interestingly, cyclosporin A (CsA) blocks NK cell death consequent to interaction with target cells or with sHLA-I, without affecting the activation of cytolysis. This would indicate that CsA can maintain NK cell-dependent innate immunity by prolonging NK cell survival in an hostile environment in the presence of sHLA-I or target cells.
authors.affiliation: Laboratory of Experimental Oncology D, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132-Genoa, Italy. alessandro.poggi@istge.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poggi
authors.forename: Maria Raffaella
authors.initials: MR
authors.lastname: Zocchi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D016572:Cyclosporine