| Project/Area Number |
12557029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Immunology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAMURA Kazuo Tohoku Univ. Graduate Sch. of Med., Dept. of Microbiol. & Immunol., Professor, 大学院・医学系研究科, 教授 (20117360)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Naoto Tohoku Univ. Graduate Sch. of Med., Dept. of Microbiol. & Immunol., Research Associate, 大学院・医学系研究科, 助手 (60291267)
ASAO Hironobu Tohoku Univ. Graduate Sch. of Med., Dept. of Microbiol. & Immunol., Associate Professor, 大学院・医学系研究科, 助教授 (80250744)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2001: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2000: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | OX40L / OX40L-transgenic mice / CD4^+ T cells / Interstitial pneumonia / Inflammatory bowel disease / OX40L欠損マウス / 自己免疫病 |
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| Research Abstract |
OX40L expressed on APCs, and its receptor, OX40 present on activated T cells, are members of the TNFR/TNF family respectively and have been located at the sites of inflammatory conditions. We have observed in OX40L-deficient mice, an impaired APC capacity, and by targeting this interaction a reduction in the symptoms of several autoimmune disorders in mice. In addition, OX40/OX40L signals are suggested to be implicated in peripheral T cell tolerance, which is a mechanism to limit autoimmunity. We have recently established OX40L transgenic (Tg) mice by using a T cell specific promoter. In these mice, failed induction of peripheral CD4^+ T-cell tolerance was observed. In addition, the OX40L-Tg mice spontaneously developed interstitial pneumonia and inflammatory bowel disease. Such autoimmune diseases were observed in OX40L-Tg mice on the C57BL/6 background but not BALB/c or DBA/1J, suggesting mice strain dependency of the disease onset. Furthermore, these diseases were completely reconstituted in Rag 2-deficient mice by introduction of OX40L-Tg CD4+ T cells and blocking of OX40/OX40L interaction completely prevented initiation of the diseases. Our findings implicate that OX40/OX4 interactions may be a vital link in a trigger of organ-specific autoimmunity.
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