2000 Fiscal Year Final Research Report Summary
Analysis of effecter mechanism of CD8^+ cells on human thyroid cells through CD40
| Project/Area Number |
09671081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Fujita Health University |
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Principal Investigator |
ITOH Mitsuyasu School of medicine, Fujita Health University Associate Professor, 医学部, 助教授 (20144066)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASAKA Akio School of medicine, Fujita Health University Professor, 医学部, 教授 (90111012)
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| Project Period (FY) |
1997 – 2000
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| Keywords | CD8 / CD40 / CD23 / IL-10 / Th2 / B cell activation / Graves disease / Autoimmune thyroid disease |
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| Research Abstract |
The present project aims at investigating T cell-dependent B cell activation and its effect on human thyroid cells. The following results were obtained ; 1) there are a reduction of CD8^+ cells in peripheral blood and increases of activated CD8^+ and CD4^+CD45RO^+memory T cells in thyroid-infiltrating cells from patients with Graves' disease. There are also increase of B cell growth factor (BCGF) and IL-10, Th2 cytokine, and a decreased release of Th-1-inducible cytokine, IL-12, resulting in an increase of IL-10/IL-12 ratio in thyroid-infiltrating lymphocytes ; 2) the stimulation with anti-CD40 monoclonal antibodies and IL-4 resulted in B cell activation demonstrated as increases of CD23^+ cells and soluble CD23. This stimulation also induced a reduction of CD8^+ cells and an increase of IL-10 in peripheral blood of Graves' disease ; 3) in thyroid cells of Graves' disease, mRNA and activity of polymerase-β were dependent on TSH and a concentration of coenzyme Q as a radical scavenger was decreased. CD40 was not detected in thyroid cells by flow-cytometry, and FAS^+ cells were not affected by B-cell activation through CD40. Further studies are under way in this signal-transduction pathway ; 4) the depletion of CD8^+ cells reduced CD28^+ cells and augmented to increase CD23^+ cells and to produce soluble CD23 in patients with Graves' disease. This depletion also increased basal release of IL-10 in cases with low basal level of it. Furthermore, the depletion of CD8^+ cells disturbed Th1 rather than Th2 or Th0. Thus, CD8^+ cells play a key role in suppressing B cell activation through CD40 and IL-4, and modifying the deviation of Th1/Th2 balance to Th2 in Graves' disease leading to the improvement of immune responses.
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[Publications] T Mano, K Iwase, R Hayashi, N Hayakawa, K Uchimura, M Makino, M Nagata, Y Sawai, N Oda, M Hamada, T Aono, A Nakai, A Nagasaka, M Itoh.: "Vitamin'E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders."Am J Med Sci. 315. 230-232 (1998)
Description
「研究成果報告書概要(欧文)」より
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