NKG2D receptor regulates human effector T-cell cytokine production

Blood. 2011 Jun 16;117(24):6571-81. doi: 10.1182/blood-2011-01-329417. Epub 2011 Apr 25.


Although innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8(+) T cells. Stimulation of CD8(+) T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3ζ, activated β-catenin and increased expression of β-catenin-induced genes, whereas T cells stimulated through the TCR or a combination of the TCR and CD28 did not. Activation by TCR and NKG2D prevented expression and production of anti-inflammatory cytokines IL-10, IL-9, IL-13, and VEGF-α in a β-catenin- and PPARγ- dependent manner. NKG2D stimulation also modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28. These data indicate that activating CD8(+) T cells through the NKG2D receptor along with the TCR modulates signal transduction and the production of anti-inflammatory cytokines. Thus, human effector T cells alter their function depending on which innate receptors are engaged in conjunction with the TCR complex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression Regulation / physiology
  • Humans
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / physiology
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K / agonists
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K / physiology*
  • Oncogene Protein v-akt / metabolism
  • Oncogene Protein v-akt / physiology
  • PPAR gamma / metabolism
  • PPAR gamma / physiology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • U937 Cells
  • beta Catenin / metabolism
  • beta Catenin / physiology


  • Anti-Inflammatory Agents
  • Cytokines
  • NK Cell Lectin-Like Receptor Subfamily K
  • PPAR gamma
  • beta Catenin
  • Oncogene Protein v-akt