Molecular analysis of the abnormal T cell function as a pathogenesis of autoimmune diseases
| Project/Area Number |
03807038
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Teikyo University School of Medicine (1992)
The University of Tokyo (1991) |
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Principal Investigator |
HIROHATA Shunsei Teikyo University, School of Medicine, Instructor, 医学部, 講師 (90189895)
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| Co-Investigator(Kenkyū-buntansha) |
沢田 哲治 東京大学, 医学部・(病)物療内科, 助手 (50235470)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | B lymphocyte / suppressor T cells / cell-to-cell contact / Anti-CD3 antibody / Ig production / DNA polymerase / ICAM-1 / LFA-1 / サプレッサ-T細胞 / ICAMー1 / LFAー1 |
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| Research Abstract |
To clarify the mechanism of abnormal T cell functions in various autoimmune diseases, we have explored the nature of human suppressor T cells in several aspects. We have utilized the culture system with immobilized mAb to CD3 molecular complex, in which B cells are very potently activated through direct interactions with stimulated T cells. We have obtained the following results. First, we have demonstrated that the suppression of B cell differentiation by human suppressor T cells requires the direct interactions between ICM-1 on activated B cells and LFA-1 on suppressor T cells. Second, we have revealed that the expression of DNA polymerase alpha in B cells is inhibited by human suppressor T cells in a reversible fashion.
Finally, we have disclosed that anti-CD3 activated CD4+ T cells as well as CD8+ T cells irrespective of their expression of CD45RA molecule are able to stimulate resting B cells to express IL-2 receptor (CD25), at the same time when they suppress the maturation of previously activated B cells, indicating that human activated T cells can simultaneously provide help as well as suppression irrespective of their phenotypes. It is rather suggested that the state of activation of B cells might be important in determining of functions of the activated T cells.
All of these results have added novel findings to the body of knowledge about human suppressor T cells, and thus may contribute to the investigation into the pathogenesis of systemic lupus erythematous, in which the deficient suppressor T cell function plays a critical role.
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Report
(3 results)
Research Products
(15 results)
