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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


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


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

February 15, 2005

Associated Grants

  • Agency: NCI NIH HHS, Id: CA89189
  • Agency: NCI NIH HHS, Id: CA95137

Mesh Terms

  • 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