title: Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway.
abstract: The ability of natural-killer cells to regulate adaptive immunity is not well understood. Here we define an interaction between the class Ib major histocompatibility complex (MHC) molecule Qa-1-Qdm on activated T cells responsible for adaptive immunity and CD94-NKG2A inhibitory receptors expressed by natural-killer cells by using Qa-1-deficient and Qa-1 knockin mice containing a point mutation that selectively abolishes Qa-1-Qdm binding to CD94-NKG2A receptors. The Qa-1-NKG2A interaction protected activated CD4+ T cells from lysis by a subset of NKG2A+ NK cells and was essential for T cell expansion and development of immunologic memory. Antibody-dependent blockade of this Qa-1-NKG2A interaction resulted in potent NK-dependent elimination of activated autoreactive T cells and amelioration of experimental autoimmune encephalomyelitis. These findings extend the functional reach of the NK system to include regulation of adaptive T cell responses and suggest a new clinical strategy for elimination of antigen-activated T cells in the context of autoimmune disease and transplantation.
authors.affiliation: Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikizawa
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Miriam B F
authors.initials: MB
authors.lastname: Werneck
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D020740:Chimerin Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D020740:Chimerin Proteins; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C527057:Klrc1 protein, mouse; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma