Interleukin-27-dependent loss of CD4 T cell-memory during malaria infection
| Project/Area Number |
16K08763
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Nagasaki University |
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Principal Investigator |
KIMURA Daisuke 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (50423637)
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| Research Collaborator |
YUI Katsuyuki
YOSHIDA Hiroki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | マラリア / 免疫記憶 / 抑制 / T細胞 / IL-27 / 記憶CD4T細胞 / アポトーシス / 記憶B細胞 / 特異抗体 / CD4T細胞 |
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| Outline of Final Research Achievements |
To examine the response of malaria-antigen specific CD4+ T cells, we used PbT-II mice that express TCR specific for the malaria antigen. C57BL/6 and Il27raKO mice were adoptively transferred with CD4+ T cells from PbT-II and Il27raKOPbT-II mice, respectively, infected with PbA and were cured by the drug treatment. One month later, Il27raKOPbT-II cells were maintained in Il27raKO mice and showed memory responses, while PbT-II cells almost disappeared from the spleen of C57BL/6 mice, confirming the effect of IL-27 on the survival of memory CD4+ T cells after malaria infection. When the mice were re-challenged with PbA, IL-27p28KO mice showed little parasitema, and their CD4+ T cells exhibited enhanced IFN-gamma response, while C57BL/6 mice exhibited high parasitemia levels. These results suggest that IL-27 inhibits the generation of memory CD4+ T cells by accelerating the apoptosis of parasite-specific CD4+ T cells during contraction phase of the immune response against PbA.
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| Academic Significance and Societal Importance of the Research Achievements |
マラリアでは免疫記憶が成立しにくいことはよく知られており、マラリアに対する有効なワクチンがこれまでに開発されていない原因の１つでもある。しかしながら、そのメカニズムは未だによくわかっていなかった。本研究成果の「マラリア原虫特異的CD4T細胞がIL-27依存的にアポトーシスを引き起こす」は、これまで明らかにされていなかった免疫記憶抑制のメカニズムの1つであると考えられ、マラリアにおける免疫記憶抑制の解除法開発へつながるものである。
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Report
(4 results)
Research Products
(18 results)
