| Project/Area Number |
22790449
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Hokkaido University |
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Principal Investigator |
MORIMOTO Junko 北海道大学, 遺伝子病制御研究所, 助教 (20451396)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 免疫記憶 / ウイルス感染 / オステオポンチン / 記憶CD8T細胞 / 二次免疫応答 / CD8T細胞 / 記憶免疫 / 二次感染 |
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| Research Abstract |
The adaptive immune system generates memory cells, which induce a rapid and robust immune response following secondary antigen encounter. Memory CD8^+T cells are a critical component of protective immunity against infections and cancers. Therefore, understanding the mechanism whereby memory CD8^+T cells are generated and maintained is important for inducing effective memory CD8^+T cell response. Recent studies have demonstrated that the inflammatory cytokine IL-12 favors the generation of terminal effector CD8^+T cells rather than memory precursor effector CD8^+T cells by regulating the expression of the transcription factor T-bet. In this study, we report that the inflammatory cytokine osteopontin(Opn) modulates memory CD8^+T cell generation during influenza virus infection. Although Opn-wild-type(Opn WT) and Opn-knockout(Opn KO) mice had similar numbers of virus-specific effector CD8^+T cells, virus-specific effector CD8^+T cells generated in Opn KO mice showed low levels of T-bet expression and an increased memory precursor cell population compared with cells generated in Opn WT mice. This resulted in the persistently increased number of memory CD8^+T cells in Opn KO mice. Studies with bone marrow-derived dendritic cells(BMDCs) demonstrated that Opn-deficiency in BMDCs results in low levels of IL-12 production in response to the stimulation with influenza virus. Thus, we hypothesize that Opn modulates the generation of memory precursor effector CD8^+T cells by regulating cytokine milieu during the acute phase of virus infection. This finding may provide new insight into the role of Opn in adaptive immune response.
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