title: Hyperthyroxinemic mice have reduced natural killer cell activity. Evidence for a defective trigger mechanism.
abstract: Natural killer (NK) activity of peripheral blood lymphocytes from hyperthyroxinemic patients (Graves' disease or thyroxine (T4)-treated) is severely depressed. In order to study the relationship of thyroid hormone to NK activity, a model for hyperthyroxinemia was induced in mice by addition of T4 to the drinking water. Control mice were hypothyroid (fed propylthiouracil) or normal. Serum T4 levels were elevated (within 2 wk) in mice fed thyroid hormone. Six weeks after initiation of the diets, in vitro NK activity was undetectable in the peripheral blood, spleen, or lung mononuclear cell populations harvested from hyperthyroxinemic mice. Control mice had NK activity within the normal range. Spleen cells from mice fed thyroid hormone and control mice were tested for their ability to release lytic factors (natural killer cytotoxic factors). Lymphoid cells were incubated for 20 hr with unlabeled Yac-1 cells. Supernatants were tested for their capacity to lyse 51Cr-labeled Yac-1 cells in a 20-hr chromium release assay. Unlike controls, supernatants from hyperthyroxinemic spleen cells incubated with Yac-1 targets were unable to lyse 51Cr-Yac-1 cells. The NK cells from the mice fed T4 synthesized lytic factors because nonspecific stimuli, such as 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore A23187, induced release of lytic factors capable of lysing Yac-1 targets into the media. These data support the hypothesis that excess thyroid hormone interferes with the triggering mechanism used by NK targets to cause release of lytic molecules from NK cells.
mesh_terms: D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal / Q000139:chemically induced / Q000276:immunology*; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D055646:Killer Factors, Yeast; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D011441:Propylthiouracil / Q000633:toxicity; D011506:Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*
chemical_list: D007376:Interleukin-2; D055646:Killer Factors, Yeast; D011506:Proteins; D011441:Propylthiouracil; D013974:Thyroxine