Enhanced production of gamma-interferon by thyroid-derived T cell clones from patients with Hashimoto's thyroiditis.
T lymphocytes from thyroid infiltrate and peripheral blood (PB) of four patients with Hashimoto's thyroiditis (HT) were analysed at clonal level for their ability to secrete interleukin 2 (IL-2) and gamma-interferon (gamma-IFN). As controls, T cell clones from PB of four normal donors and from spleen of two trauma victims were used. While no abnormality was found in the capacity to produce IL-2, the proportion of gamma-IFN-producing (IFN-P) T cell clones derived from HT infiltrates was significantly higher (P less than 0.0005) than that of IFN-P clones derived from normal or patient PB. Most of CD4+ and CD8+ IFN-P clones from thyroid infiltrates, as well as a proportion of CD4+ PB-derived clones of patients with HT, released higher amounts of gamma-IFN than control clones. A relationship could be demonstrated between high gamma-IFN production and natural killer (NK) activity in T cell clones from thyroid and PB of HT patients. In fact, the percentage of IFN-P clones with NK potential (NK+) was remarkably higher (P less than 0.0005) in thyroid infiltrates than in normal spleen or PB. The proportion of IFN-P NK+ clones from patient PB was also significantly increased (P less than 0.02) but, unlike thyroid-derived clones in which the majority of IFN-P NK+ clones were CD8+, most PB-derived IFN-P NK+ clones from the same patients expressed the CD4+ phenotype. Almost all thyroid NK+ clones could be triggered to produce more gamma-IFN, while gamma-IFN synthesis by NK-negative thyroid clones was comparable to that of control clones. In view of the multiple effects ascribed to gamma-IFN in the cascade of events leading to immune responses, the abnormal potential to gamma-IFN secretion shown by intrathyroidal T lymphocytes may be of importance in the pathogenesis of autoimmune thyroiditis.
D000328:Adult; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D007376:Interleukin-2; D007371:Interferon-gamma