| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
We examined lymphocyte subsets in both blood and thyroid from patients with autoimmune thyroid disease by two-color flow cytometry to identify the difference in immunological background that allows the stimulative and destructive changes in thyroid tissue in Hashimoto's and Graves' diseases, respectively. In Peripheral blood, both Tgammadelta (CD3^+TCRalphabeta^-TCRgammadelta^+) cells and CD8^+ cells (which include cytotoxic T cells) decreased in active Hashimoto's disease with destructive thyrotoxicosis and CD5^+B (CD5^+CD19^+) cells increased markedly in active Graves' disease with stimulative thyrotoxicosis. In thyroid gland, proportions of cytotoxic T (CD8^+CD11b^-) cells and CD5^-B (CD5^+CD19^-) cells were higher in Hashimoto's and Graves' diseases, respectively, as compared with those in the peripheral blood. Proportions of CD5^-B cells, helper T (CD4^+Leu8^-) cells and germinal center T (CD4^+CD57^+) cells were higher and proportions of suppressor-inducer T (CD4^+Leu8^+) cells,
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suppressor T (CD8^+CD57^+ or CD8^+CD11b^+) cells, and NK (CD16^+CD57^+) cells were lower than in the blood in both diseases. Tgammadelta cells were present similarly in both blood and thyroid. Unexpectedly, double negative T (CD3^+TCRalphabeta^<+/->TCRgammadelta^-CD4^-CD8^-) cells and double positive T (CD4^+CD8^+) cells were present in thyroid tissues of both diseases. Furthermore, we examined which B cell subset produces thyroid autoantibodies by using ELISPOT assay. CD5^-B cells produced IgG classes of thyroid autoantibodies (thyroid microsomal antibodies and thyroglobulin antibodies). IgM classes of thyroid autoantibodies were produced by both CD5^+B and CD5^-B cells even in normal subjects, when stimulated by B cell mitogen. These findings suggest that 1) cytotoxic T cells and CD5^+B cells are important for the different pathological features in Hashimoto's and Graves' diseases, respectively, 2) an imbalance in the numbers of regulatory T cells and NK cells that had appeared in the thyroid resulted in the proliferation of CD5^-B cells, which produce thyroid autoantibodies, and 3) intrathyroidal double negative T (CD3^+TCRalphabeta^<+/->CD4^-CD8^-) and double positive T (CD4^+CD8^+) cells may be related to the pathogenesis of autoimmune thyroid disease. Less
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