title: NKG2D receptor regulates human effector T-cell cytokine production.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Bldg, One Medical Center Drive, Lebanon, NH 03756, USA.
authors.forename: Amorette
authors.initials: A
authors.lastname: Barber
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sentman
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000502:physiology; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000819:agonists / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D020298:U937 Cells; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D055655:NK Cell Lectin-Like Receptor Subfamily K; D047495:PPAR gamma; D051176:beta Catenin; D051058:Oncogene Protein v-akt