Phenotypic analyses and concanavalin-A-induced suppressor cell dysfunction of intrathyroidal lymphocytes from patients with Graves' disease.
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+CD11b+ 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.
Ueki
Y
Y
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Otsubo
T
T
Kawabe
Y
Y
Shimomura
C
C
Matsunaga
M
M
Tezuka
H
H
Nakao
H
H
Kawakami
A
A
Izumi
M
M
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D008297:Male; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology*; D013961:Thyroid Gland / Q000276:immunology*
D000911:Antibodies, Monoclonal; D003208:Concanavalin A