| Project/Area Number |
08457107
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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 |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
KIKUTANI Hitoshi Research Institute for Microbial Diseases, Osaka University Professor, 微生物病研究所, 教授 (80161412)
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| Co-Investigator(Kenkyū-buntansha) |
YASUI Teruhito Faculty of Medicine, Toyama Medical and Pharmaceutical University Assistant Prof, 医学部, 助手 (60283074)
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| Project Period (FY) |
1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1996: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | CD40 / CD40 ligand / cell to cell interaction / Th1 T cell / Th2 T cell / infection / transgenic mice / gene-targeted mice / クラススイッチ |
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| Research Abstract |
The CD40-CD40 ligand (CD40L) interaction is known to be essential for humoral immune responses. It has also been recently suggested that CD40 on antigen presenting cells play an important role in T cell activation. To elucidate a role of CD40 in T cell activation/differentiation, we studied immune responses of CD40-deficient mice against Leishmania major, a resolution of which is known to be dependent on a Th1 T cell response. Our results demonstrated that CD40-deficient mice were susceptible to L.major infection.
Furthermore, it turned out that the mutant mice mounted a Th2 response to the parasites instead of a Th1 response because of an absence of CD40-dependent IL-12 production by antigen-presenting cells. The role of CD40 in generation of effector T cells could be demonstrated in vitro. T cells from OVA-specific TCR transgenic mice were stimulated with OVA peptides in the presence of CD40-positive or negative APC.Certain concentrations of peptides could induce generation of IFN-g producing Th1 cells in the presence of CD40-positive APC but not in the presence of CD40-negative APC while IL-4 producing Th2 cells could be induced by both CD40-positive and CD40-negative APC with appropriate concentrations of peptides. Moreover, addition of IL12 could rescue the generation of Th1 cells in the presence of CD40-negative APC.These results suggest that CD40-dependent IL-12 production by APC may be critical in generation of Th1 effector cells.
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