Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells.
CD8+ T cells require a signal through a costimulatory receptor in addition to TCR engagement to become activated. The role of CD28 in costimulating T cell activation is well established. NKG2D, a receptor found on NK cells, CD8+ alphabeta-TCR+ T cells, and gammadelta-TCR+ T cells, has also been implicated in T cell costimulation. In this study we have evaluated the role of NKG2D in costimulating mouse and human naive and effector CD8+ T cells. Unexpectedly, in contrast to CD28, NKG2D engagement by ligand or mAb is not sufficient to costimulate naive or effector CD8+ T cell responses in conventional T cell populations. While NKG2D did not costimulate CD8+ T cells on its own, it was able to modify CD28-mediated costimulation of human CD8+ T cells under certain contitions. It is, therefore, likely that NKG2D acts as a costimulatory molecule only under restricted conditions or requires additional cofactors.
Ehrlich
Lauren I Richie
LI
Department of Microbiology and Immunology and The Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
Ogasawara
Kouetsu
K
Hamerman
Jessica A
JA
Takaki
Rayna
R
Zingoni
Alessandra
A
Allison
James P
JP
Lanier
Lewis L
LL
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D003432:Cross-Linking Reagents / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D016192:Resting Phase, Cell Cycle / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D003432:Cross-Linking Reagents; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma