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Dysfunction of Suppressor T Cells in Thyroid Glands from Patients with Graves' Disease

First Department of Internal Medicine, Nagasaki University School of Medicine Nagasaki, Japan
Ito Hospital (N.I., K.I.) Tokyo, Japan

Address requests for reprints to: Dr. Shigenobu Nagataki, First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852, Japan.

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 x 10⁴ B (PB¹ or TG) cells, 2 x 10⁴ CD4⁺ (PB or TG) cells, and 5 x 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.

¹The following abbreviations are used: B (PB) cells, B cells isolated from peripheral blood; B (TG) cells, B cells isolated from thyroid gland; CD4⁺ cells, helper/suppressor inducer T cells; CD8⁺ cells, suppressor/cytotoxic T cells; CD4⁺ (PB) cells, CD4⁺ cells isolated from peripheral blood; CD4⁺ (TG) cells, CD4⁺ cells isolated from thyroid gland; CD8⁺ (PB) cells, CD8⁺ cells isolated from peripheral blood; CD8⁺ (TG) cells, CD8⁺ cells isolated from thyroid gland.

Received October 8, 1986.