| Project/Area Number |
03044130
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokai University, School of Medicine |
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Principal Investigator |
HABU Sonoko Dept. of Medicine Tokai University, School of Medicine, 生体防御機構系・免疫学, 教授 (30051618)
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| Co-Investigator(Kenkyū-buntansha) |
DENNIS Y LOH ワシントン大, 医・ハワートヒューズ医学研究所・免疫学, 教授
NISHIMURA Takashi Dept. of Medicine Tokai University, School of Medicine, 生体防御機構系・免疫学, 助教授 (30143001)
LOH Dennis Y. Howard Hughes Medical Institute Research Laboratories Washington University Scho
LOH Dennis Y ワシントン大学, 医学部・ハワードヒューズ医学研究所
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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 |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | autoimmune disease / T cell antigen receptor(TCR) / apoptosis / self-reactive T cells / thymic stromal cells / intrathymic development / transgenic mouse / thymus / T細胞抗原レセプタ- / クロ-ン選択機構 / 胸線ストロ-マ細胞 / 胸線内分化 |
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| Research Abstract |
In autoimmune diseases, certain T cell clones react to self-components, resulting in the abnormal reactions for tissues. In normal animals or human beings, such T cells reacting self-compomets are known to be deleted in the developing pathway in the thymic environment but the deletion mechanism of self-reactive T cells remained unclear. Thus, the study of this mechanism on molecular levelis important for understanding the occurrence of autoimmune diseases. In this project of US-Japan collaboration, we tried to establish an appropriate experimental system in which development of a particular T cells by interaction of thymic stromal cells is examined. For obtaining thymocytes of a particular T cell clone at various developing stages in physiological condition, we tried to produce T cell antigen receptor (TCR) transgenic mice. At the same time, we tried to establish thymic stromal cell clones which are capable of inducing immature thymocytes into mature ones.
During the period of this project, we succeeded to obtain TRC transgenic mice in which the majority of T cells recognize OVA. We also established a thymic stromal cell clones possessing inductive functions for thymocyte development. When the thymocytes from TCR transgenic mice were cultured on the stromal cellclone in the presence of OVA. specific deletion of thymocytes were demonstration a CD4^+CD8^+ thymocyte developing stage. DNA fragmentation of the thymocytes were also induced by adding OVA. These results indicate that immature thymocytes are deleted in the thymus by apoptosis when they recognize the antigens, which are self-components in physiological conditions. Using our established system, we are planning to identify the moleculres which are involved in inducing deletion of immature T cells reacting to antigens in the thymus.
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