Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells.

Journal:

J. Immunol. 2005 Feb

Authors:

Ehrlich LI, Ogasawara K, Hamerman JA, Takaki R, Zingoni A, Allison JP, Lanier LL

Abstract

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
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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.[less]

Mesh Headings:

Adjuvants, Immunologic, Animals, Antibodies, Monoclonal, Antigens, CD28, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Cells, Cultured, Coculture Techniques, Cross-Linking Reagents, Cytotoxicity Tests, Immunologic, G0 Phase, 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