title: CD3+CD8+NKG2D+T Lymphocytes Induce Apoptosis and Necroptosis in HLA-Negative Cells via FasL-Fas Interaction.
abstract: An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4+CD25+lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8+lymphocytes. We show that after a tumor antigen contact the IL-2 activated CD8+lymphocytes acquire ability to lyse tumor cells bearing this antigen. However, activation of the CD8+lymphocytes in the absence of antigen causes appearance of a cytotoxic population of CD8+NKG2D+lymphocytes, which are able to lyse HLA-negative cancer cells that have lost the classic mechanism of antigen presentation. These cells recognize the noncanonical MicA antigen on the surface of HLA-negative K562 cells but kill them via the FasL-Fas interaction, as do cytotoxic T lymphocytes. FasL presented on the lymphocyte surface can trigger both apoptosis and necroptosis. Unlike in the case of TNFR1, another cell death receptor, no switching to alternative processes has been observed upon induction of Fas-dependent cell death. It may well be that the apoptotic and necroptotic signals are transduced separately in the latter case, with the ability of FasL+lymphocytes to induce necroptosis allowing them to kill tumor cells that escape apoptosis. J. Cell. Biochem. 118: 3359-3366, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
authors.forename: Olga K
authors.initials: OK
authors.lastname: Ivanova
authors.affiliation: Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Sharapova
authors.affiliation: Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Romanova
authors.affiliation: Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Soshnikova
authors.affiliation: Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
authors.forename: Lidia P
authors.identifier: 0000-0002-5164-2260
authors.initials: LP
authors.lastname: Sashchenko
authors.affiliation: Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Yashin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D053222:Fas Ligand Protein / Q000276:immunology*; D006680:HLA Antigens; D006801:Humans; D007111:Immunity, Cellular; D020014:K562 Cells; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009369:Neoplasms / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: D017252:CD3 Complex; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006680:HLA Antigens; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D019014:fas Receptor
keywords: APOPTOSIS; CYTOTOXITY; Fas; FasL; HUMAN LYMPHOCYTES; NECROPTOSIS; NKG2D