| Project/Area Number |
15591056
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Saga University (2004)
佐賀医科大学 (2003) |
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Principal Investigator |
TADA Yoshifumi Saga Medical School, Internal Medicine, Assistant professor, 医学部, 講師 (70284627)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASAWA Kohei Saga Medical School, Internal Medicine, professor, 医学部, 教授 (00108721)
KOARADA Syuichi Saga Medical School, Internal Medicine, Assistant professor, 医学部, 助手 (50304887)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | inducible costimulator / costimulatory molecule / autoimmunity / autoantibody / nephritis / lupus |
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| Research Abstract |
1.Generation of icos-deficient MRL/lpr mice
Icos-deficient mice were backcrossed into MRL/lpr mice for seven generations. Icos +/- mice were intercrossed, and icos+/+ MRL/lpr and icos-/- MRL/lpr mice were generated.
2.Lymphoproliferation and splenomegaly
Icos-/-MRL/lpr mice showed less severe lymphadenopathy, but similar level of splenomegaly as compared with those in icos+/+ MRL/lpr mice.
3.Analysis of spleen cells
In the spleen from iocs-/- MRL/lpr mice, B220-T cells and CD4+ T cells were reduced as compared with that from control MRL/lpr mice. Regarding splenic CD4+ T cells, the reduction of memory T cells and B22O-CD4+ T cells were noted in icos-/- MRL/lpr mice. The intracellular cytokine staining of CD4+ T cells showed that the ratio of IFN-gamma-positive calls/IL-4-positive cell was decreased in icos-/- MRL/ipr mice. The result indicates that in CD4+ T cells from icos-/- MRL/lpr mice, cytokine balance is biased to Th2 as compared with that in icos+/+ MRLlpr mice
4.Autoantibodies
In icos-/- MRL/lpr mice, serum anti-dsDNA antibody levels of IgG1,IgG2a,and IgM subclasses, but not IgG3 subclass were decreased as compared with those in icos+/+ MRL/lpr mice.
5.Cytokine levels
In icos-/- MRL/lpr mice, serum levels of MCP-1 and IL-12p70 were lower than those in icos+/+ MRL/lpr mice.
6.Glomerulonephritis
The severity of glomerulonephritis was not different between icos-/- MRL/lpr mice and icos+/+ MRL/lpr mice. However, perivascular and interstitial infiltration of inflammatory cells was completely abolished in icos-/- MRL/lpr mice.
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