| Project/Area Number |
14370164
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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 | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Kobe University |
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Principal Investigator |
KUMAGAI Shunichi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00153346)
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| Co-Investigator(Kenkyū-buntansha) |
HONJO Tasuku Kobe University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (80090504)
SAURA Ryuichi Kobe University, School of Medicine, Assistant Professor, 医学部, 助教授 (10252769)
KOSHIBA Masahiro Kobe University, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (70301827)
KAWANO Seiji Kobe University, School of Medicine, Lecturer, 医学部附属病院, 講師 (20351512)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | PD-1 / PD ligand / rheumatoid arthritis / co-stimulatory molecule / synovial cell / arthritis / collagen-induced arthrits / コラーゲン誘導関節炎 / 関節液 |
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| Research Abstract |
The aim of the investigation is to clarify whether (1) the abnormalities of the inhibitory co-stimulatory system PD-1/PD-L ligand (PD-L1), which we first described, exist in rheumatoid arthritis (RA) and (2) if so, the abnormalities of PD-1/PD-L system result in the induction of RA. The followings are our achievements ;
1. Synovial fluid (SF) from RA patients contained PD-1+CD4+T cells, while such cells were essentially not detected in peripheral blood or SF from osteoarthritis patients. These cells were considered to have the inhibitory function since they also expressed CTLA-4 and were positive for the intracelluar IL-10. Interferon (IFN)-gamma strongly induced the cell-surface expression of PD-L1, but not the other co-stimulatory molecules such as B7.1 and B7.2, on cultivated synovial cells in vitro.
2. The expression of PD-1 and PD-L1 in articular tissue of RA patients was examined immunohistochemically using the newly developed monoclonal antibodies. PD-L1 was strongly expressed on the surface layer cells of synovial tissue and the endothelial cells. PD-L1 was also expressed on the majority of infiltrated cells expressed PD-L1. It is currently under examination by the double staining method on frozen samples what kind of cells express PP-I and which cytokines these cells produce.
3. On collagen induced arthritis (CIA) mice, synovial cells were positive for PD-L1 while some of the bone marrow cells were PD-L2 positive. Administration of anti PD-L1 antibodies to the CIA mice tended to inhibit the onset of arthritis.
4. PD-1 knockout (KO) mice are known to develop arthritis naturally, and it is highly, possible that CIA on these mice is severer than CIA on wild type mice due to the lack of PD-1 system, which again indicate the involvement of PD-1/PD-L1 system on the etiology of RA. The process to make the KO mice specific pathogen free is currently on-going.
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