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.
Pubmed ID: 15699119 RIS Download
Adjuvants, Immunologic | Animals | Antibodies, Monoclonal | Antigens, CD28 | CD8-Positive T-Lymphocytes | Cell Line, Tumor | Cells, Cultured | Coculture Techniques | Cross-Linking Reagents | Cytotoxicity Tests, Immunologic | Humans | Interferon-gamma | Ligands | Lymphocyte Activation | Melanoma, Experimental | Mice | Mice, Inbred C57BL | Mice, Inbred DBA | Mice, Transgenic | NK Cell Lectin-Like Receptor Subfamily K | Receptors, Antigen, T-Cell | Receptors, Immunologic | Receptors, Natural Killer Cell | Resting Phase, Cell Cycle