Activation of V gamma 9V delta 2 T cells by NKG2D.
Human Vgamma9 Vdelta2 T cells recognize phosphorylated nonpeptide Ags (so called phosphoantigens), certain tumor cells, and cells treated with aminobisphosphonates. NKG2D, an activating receptor for NK cells, has been described as a potent costimulatory receptor in the Ag-specific activation of gammadelta and CD8 T cells. This study provides evidence that Vgamma9 Vdelta2 T cells may also be directly activated by NKG2D. Culture of PBMC with immobilized NKG2D-specific mAb or NKG2D ligand MHC class I related protein A (MICA) induces the up-regulation of CD69 and CD25 in NK and Vgamma9 Vdelta2 but not in CD8 T cells. Furthermore, NKG2D triggers the production of TNF-alpha but not of IFN-gamma, as well as the release of cytolytic granules by Vgamma9 Vdelta2 T cells. Purified Vgamma9 Vdelta2 T cells kill MICA-transfected RMA mouse cells but not control cells. Finally, DAP10, which mediates NKG2D signaling in human NK cells, was detected in resting and activated Vgamma9 Vdelta2 T cells. These remarkable similarities in NKG2D function in NK and Vgamma9 Vdelta2 T cells may open new perspectives for Vgamma9 Vdelta2 T cell-based immunotherapy, e.g., by Ag-independent killing of NKG2D ligand-expressing tumors.
Rincon-Orozco
Bladimiro
B
Institut für Virologie und Immunobiologie, Julius-Maximilians Universität, Würzburg, Germany.
Kunzmann
Volker
V
Wrobel
Philine
P
Kabelitz
Dieter
D
Steinle
Alexander
A
Herrmann
Thomas
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003594:Cytoplasmic Granules / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000097:blood; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016207:Cytokines; C120528:HCST protein, human; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell