1988 Fiscal Year Final Research Report Summary
The Studies of Pathogenesis of Graves' Disease
| Project/Area Number |
61480252
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAGATAKI Shigenobu The First Department of Internal Medicine, 医学部, 教授 (70010311)
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| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Katsumi The First Department of Internal Medicine, 医学部, 助手 (30128160)
IZUMI Motomori The First Department of Internal Medicine, 医学部, 講師 (80039552)
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| Project Period (FY) |
1986 – 1987
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| Keywords | バセドウ病の成因 |
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| Research Abstract |
Much attention has recently been drawn to the role of lymphocytes and lymphokines in the pathogenesis of Graves' disease. Therefore, the subsets and functions of lymphocytes in Graves' thyriod and peripheral blood were studied and the action of Interferon gamma (INFgamma) on thyrocytes was investigated.
T cell subsets were analized in patients with Graves' disease. The ratios of helper/inducer T cells (CD4^+) and of suppressor/cytotoxic T cells (CD8^+) to total T cells (CD3) were similar between the thyroid and the peripheral blood. In contrast, both the ratios of activated CD4^+ to CD4^+ and activated CD8^+ to CD8^+ are increased in the thyroid compared with those in the peripheral blood. The ratio of helper T cell (CD4^+2H4^-) to CD4^+ is increased and the ratio of suppressor inducer T cell (CD4^+2H4^-) to CD4^+ is decreased in the thyroid compared with those in the peripheral blood.
CD8^+ function was studied. B cell and CD4^+ were incubated with or without CD8^+ and the supernatant w
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as assayed for IgG. Peripheral blood CD8^+ inhibited IgG production significantly but intrathyroidal CD8^+ did not. The inhibitory activity peripheral blood CD8^+ were found to be lower in the culture system of thyroidal B cell and CD4^+ than that of peripheral blood B cell and CD4^+, suggesting that the suppressor function of CD4^+ may be weak in the thyroid.
These results may suggest that suppressor circuits may be impared in Graves' thyroid with autoantibody production resulting.
INFgamma is one of lymphokines which madiate the action of lymphocytes. When INFgamma was incubated with cultured thyrocytes the expression of DR antigen was induced on the thyrocyte surface. These DR positive thyrocytes found to stimulate T cells to increase uptake of ^3H thymidine. In contrast, when INFgamma was added in the culture system where cultured thyrocyres secret T and thyroglobulin in media in response to TSH stimulation, INFgamma significantly inhibit thyrocytes to secret T_3 and thyroglobulin. The site of this action of INFgamma was considered to be the steps both before and after cAMP production since INFgamma inhidited cAMP production stimulated by TSH and T_3 and thyroglobulin secretion by Dibutyl cAMP. Less
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