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Phenotypic Analyses and Concanavalin-A-Induced Suppressor Cell Dysfunction of Intrathyroidal Lymphocytes From Patients With Graves' Disease

First Department of Internal Medicine, Nagasaki University School of Medicine Nagasaki 852
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.

The expression of phenotypic markers and Concanavalin-A-induced suppressor activity was compared among mononuclear cells isolated from thyroid glands and peripheral blood of thionamide-treated patients with hyperthyroid Graves’ disease and peripheral blood from normal subjects. Intrathyroidal lymphocytes were obtained by two different methods (TG-1 and TG-2 cells), gradient centrifugation of supernatants of minced thyroid tissue and overnight culture of thyroid debris after mechanical disaggregation and enzymatic digestion, respectively. The percentages of CD3⁺ cells (all mature T cells) among peripheral blood and TG-1 and TG-2 cells from Graves’ patients were similar, but the percentages of B1⁺ cells (pan B cells) among the TG-1 and TG-2 cells were markedly increased compared to that in peripheral blood. The percentages of CD4⁺ cells among the TG-1 and TG-2 cells were significantly less than that in peripheral blood. The percentages of CD4⁺2H4⁺ cells among CD4⁺ cells in TG-1 and TG-2 cells also were significantly less than that in peripheral blood. The percentage of CD4⁺4B4⁺ cells among CD4⁺ cells in thyroid glands was markedly higher than that in peripheral blood. The percentages of CD8⁺ cells and CD8⁺CD11b^– cells (cytotoxic T cells) in thyroid glands were significantly higher than those in peripheral blood from Graves’ patients and peripheral blood from normal subjects. The CD8⁺CD1b⁺ cells were subdivided into two subpopulations on the basis of CD8 antigen density. The percentage of dull CD8⁺CD11b⁺ cells (natural killer cells) among TG-2 cells was lower than that in peripheral blood, but there was no significant difference in bright CD8⁺CD11b⁺ cells (suppressor-effector T cells) between thyroid glands and peripheral blood. The percent suppression induced by Concanavalin-A in both TG-1 and TG-2 cells was significantly decreased compared with that in peripheral blood. These results suggest that impairment of suppressor cell activity and an increased number of B cells exist in thyroid glands of patients with Graves’ disease compared to those in peripheral blood. It, thus, appears likely that both B cell hyperactivity and suppressor T cell dysfunction may induce excess production of autoantibodies in the thyroid glands of such patients.

¹The following abbreviations are used: CD3⁺ cells, all mature T cells; CD4⁺ cells, helper/inducer T cells; CD8⁺ cells, suppressor/ cytotoxic T cells; B1⁺ cells, pan B cells: CD4⁺2H4⁺ cells, suppressor-inducer T cells; CD4⁺4B4⁺ cells, helper T cells; CD8⁺CD11b^– cells, cytotoxic T cells; CD8⁺CD11b⁺ cells, suppressor T cells; bright CD8⁺CD11b⁺ cells, suppressor-effector T cells; dull CD8⁺CD11b⁺ cells, natural killer cells; TG-1 cells, intrathyroidal mononuclear cells isolated frrom the supernatants after mechanical disaggregation of the tissue; TG-2 cells, intrathyroidal mononuclear cells isolated from the supernatants of the overnight cultures of thyroid debris after mechanical disaggregation and enzymatic disgestion.

Received November 18, 1987.