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YUKITAKA UEKI, KATSUMI EGUCHI, TAKAAKI FUKUDA, TOSHIO OTSUBO, YOJIRO KAWABE, CHIKAKO SHIMOMURA, MAYUMI MATSUNAGA, HIROSHI TEZUKA, NAOFUMI ISHIKAWA, KUNIHIKO ITO, SHIGENOBU NAGATAKI, Dysfunction of Suppressor T Cells in Thyroid Glands from Patients with Graves' Disease, The Journal of Clinical Endocrinology & Metabolism, Volume 65, Issue 5, 1 November 1987, Pages 922–928, https://doi.org/10.1210/jcem-65-5-922
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To investigate the suppressor function of intrathyroidal (TG) T cells in Graves' disease, the percentage of suppressor T cell subsets and the suppressor function of TG and peripheral blood (PB) lymphocytes in Graves' disease were compared by determining the in vitro production of immunoglobulin G (IgG) in reconstituted mixtures of separated B, CD4+ (helper/suppressor-inducer T), and CD8+ (suppressor/cytotoxic T) cells. TG lymphocytes were obtained by gradient centrifugation of the supernatants of minced thyroid tissues. T Cells were separated by E-rosette formation, and CD4+ and CD8+ cell-rich populations were separated by a panning method using monoclonal anti-CD8 antibody. Mixtures of 5 × 104 B (PB1 or TG) cells, 2 × 104 CD4+ (PB or TG) cells, and 5 × 103 macrophages (PB or TG) were cultured with various numbers of CD8+ (PB) or CD8+ (TG) cells for 7 days with pokeweed mitogen, and IgG synthesis was determined by solid phase RIA. T Cell subpopulations were quantitated by a direct immunofluorescence method using monoclonal anti-CD3, anti-CD4, and anti-CD8 antibodies. There was no difference in the percentages of CD8+ cells among total T cells between thyroid glands and peripheral blood from Graves' disease patients [mean PB, 39.8 ± 9.8% (±sd); TG, 42.5 ± 13.8%; n = 10]. IgG production by mixtures of B and CD4+ cells isolated from peripheral blood was not different from that by cells isolated from thyroid glands [mean PB, 1635 ± 248 (±se) ng/mL; TG, 1081 ± 128 ng/mL; n = 19; P = NS]. The nonspecific suppressor activity of thyroid gland CD8+ cells was less than that of CD8+ (PB) cells [percent suppression of IgG production by mixtures of B (PB) and CD4+ (PB) cells, 12.5% vs. 57.0% (P < 0.01); by mixtures of B (TG) and CD4+ (TG) cells, 5.8% vs. 38.9% (P < 0.01)]. The suppressor-inducer function of CD4+ (TG) cells was also decreased compared with that of CD4+ (PB) cells. These results suggest that the impairment of suppressor cell activity may lead to excessive production of autoantibody in thyroid glands from patients with Graves' disease.
