Project/Area Number |
62480167
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Functional basic dentistry
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Research Institution | Kyushu University |
Principal Investigator |
YOSHIKAI Yasunobu Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (90158402)
|
Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Kazuto Medical Institute of Bioregulation, Kyushu University, Assistant Professor, 生体防御医学研究所, 助手 (50117165)
姫野 国祐 九州大学, 生体防御医学研究所, 助教授 (50112339)
|
Project Period (FY) |
1987 – 1989
|
Project Status |
Completed (Fiscal Year 1989)
|
Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥5,100,000 (Direct Cost: ¥5,100,000)
|
Keywords | T cells / T cell receptor / T cell differentiation / Thymus / bone marrow chimera / Thymus-grafted nude mice / T細胞抗原レセプター / 放射線照射骨髄移植キメラマウス / 胸腺移植ヌードマウス / T細胞抗原レセプター(α,β,γ,δ鎖)遺伝子 / 骨髄キメラマウス / 長期培養骨髄細胞 |
Research Abstract |
T cell precursors derived from hematopoietic stem cells proliferate and differentiate in thymus, where T cells with self-MHC specificities are positively selected (positive selection) and T cells with a high affinities for self-antigens are tolerized(negative selection). These selections are carried out on the basis of their T cell receptors (TcR). To elucidate the molecular mechanism of T cell differentiation, we have investigated the expression of TcR gene in bone marrow(BM), thymus and peripheral lymphoid tissues of mice. 1. BM --- The use of the long-term cultured bone marrow (LTBM) cells provided a pertinent source of cells for investigating the early phase of T cell differentiation before migration to the thymus. Our study with athymic nde mice and 1pr/1pr mice indicated abnormal rearrangememnts of TcR genes in the LTBM cells, suggesting that T cell precursors in BM of these mice may be different in quantity and/or quality from those in normal mice. 2. Thymus --- Radiation BM chimeras have been used as an experimental model for investigation of mechanisms of selective events in thymxis of adult mice. We have found that both T cells bearing TcR capable of recognizing host- and donor phenotypes are deleted in the thymus of radiation BM chimeras. 3. Peripheral lymphoid tissues --- The cellular basis of tolerant induction has been investigated in nude mice grafted with fetal thymus. Thymic epithelium have a capacity to induce tolerance to MHC class II but not to Mls-encoded antigens.
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