| Project/Area Number |
17590332
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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 |
Experimental pathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
ISHIZU Akihiro Hokkaido University, School of Medicine, Associate Professor, 医学部, 助教授 (60321957)
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 直美 北海道大学, 大学院・医学研究科, 客員研究員 (40374251)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Necrotizing arteritis / Animal model / Autoimmunity / Thymus / T-cell |
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| Research Abstract |
We previously showed that thymus plays a critical role in the pathogenesis of necrotizing arteritis occurred in env-pX rats (transgenic rats carrying the LTR-env-pX gene of human T-cell leukemia virus type-1). T-cells autoreactive with the self vasculature might be generated during the interaction of progenitor T-cells derived from the bone marrow with the thymic framework expressing the env-pX transgene, and these autoreactive T-cells induced necrotizing arteritis in env-pX rats. Corresponding to the concept, we established T-cells autoreactive with wild-type vascular endothelial cells, from env-pX rats. Intravenous injection of these T-cell, designated as PC4, induced vasculitis in the lung of syngenic but not allogenic recipients. PC4 contained oligoclonal Thl-type T-cells expressing MHC class II and CD80, and their proliferation was completely inhibited by the anti-MHC class II antibody. Rat vascular endothelial cells did not express MHC class II even when co-cultured with PC4. On the other hand, PC4 exhibited the phagocytotic activity. These findings suggest that PC4 proliferated autologously in the co-culture system. Since MHC class II-expressing cells were present in the vascular endothelium in the lung, PC4 might recognize a certain autoantigen presented on the MHC class II, proliferate, and injure the vasculature by a direct and/or indirect mechanism.
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