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

J Immunol. 2005 Feb 15;174(4):1922-31. doi: 10.4049/jimmunol.174.4.1922.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / physiology
  • Animals
  • Antibodies, Monoclonal / metabolism*
  • CD28 Antigens / metabolism
  • CD28 Antigens / physiology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Coculture Techniques
  • Cross-Linking Reagents / metabolism
  • Cytotoxicity Tests, Immunologic
  • Humans
  • Interferon-gamma / biosynthesis
  • Ligands
  • Lymphocyte Activation / immunology*
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism*
  • Receptors, Immunologic / physiology
  • Receptors, Natural Killer Cell
  • Resting Phase, Cell Cycle / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • CD28 Antigens
  • Cross-Linking Reagents
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Interferon-gamma