NKG2D is a costimulatory receptor for human naive CD8+ T cells

J Immunol. 2005 Apr 15;174(8):4480-4. doi: 10.4049/jimmunol.174.8.4480.

Abstract

In humans, all alpha beta CD8+ T cells express NKG2D, but in mouse, it is only expressed by activated and memory CD8+ T cells. We purified human naive CD8+ T cells to show that NKG2D serves as a costimulatory receptor for TCR induced Ca2+ mobilization and proliferation. The resulting effector cells are skewed toward a type 1 phenotype and produce high levels of IFN-gamma and TNF-alpha. NKG2D ligands, MHC class I chain-related (MIC)A, MICB, and UL16-binding proteins are expressed on the proliferating cells and NKG2D is down-regulated. The addition of the homeostatic cytokines IL-7 and IL-15 to the culture medium not only enhances proliferation but also counteracts the down-regulation of NKG2D, more so than the addition of IL-2. These results indicate that NKG2D can regulate the priming of human naive CD8+ T cells, which may provide an alternative mechanism for potentiating and channeling the immune response.

MeSH terms

  • Animals
  • Base Sequence
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Calcium Signaling
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Proliferation
  • DNA, Complementary / genetics
  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • In Vitro Techniques
  • Intercellular Signaling Peptides and Proteins
  • Interferon-gamma / biosynthesis
  • Intracellular Signaling Peptides and Proteins
  • Killer Cells, Natural / immunology
  • Ligands
  • Lymphocyte Activation
  • Membrane Proteins
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Immunologic / immunology*
  • Receptors, Natural Killer Cell
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Carrier Proteins
  • DNA, Complementary
  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • MHC class I-related chain A
  • MICB antigen
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Tumor Necrosis Factor-alpha
  • ULBP1 protein, human
  • ULBP2 protein, human
  • ULBP3 protein, human
  • Interferon-gamma