2012 Fiscal Year Final Research Report
How MHC class II molecules promote memory CD8 T cell homeostasis
| Project/Area Number |
23790549
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Kyoto University |
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Principal Investigator |
SETOGUCHI Ruka 京都大学, 医学研究科, 特定准教授 (50415204)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 免疫学的記憶 |
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| Research Abstract |
Memory CD8 T cells are long-lived antigen (Ag)-specific CD8 T cells which respond quickly, proliferate robustly, and exert effector functions faster than naive CD8 T cells upon reencounter with the specific Ags. Memory CD8 T cells are maintained at a stable size over a long period of time, but the mechanisms by which their population size is maintained remain elusive. It has been proposed that the maintenance of memory CD8 T cells depends on “CD4 T cell help”, based on the observation that CD8+ T cells which have been primed with Ags in wild-type (WT) mice survive poorly when transferred into MHCII-/- hosts as comparedto WT hosts. Our results clearly show that the impaired maintenance of memory CD8 T cells in MHCII-/- mice is not due to the absence of CD4+ helper T cells. This was shown by transferring Ag-primed CD8+ T cells into WT mice treated with the anti-CD4 GK1.5 mAb, or CD4-/- mice, or ThPOK mutant mice, all of which lack functional CD4+ helper T cells. We also found that MHCII molecules expressed by hematopoietic cells, not by non-hematopoietic cells, are required for memory CD8 T cell maintenance. The mRNA expression levels of IL-7 and IL-15, cytokines reported tobe important for memory CD8 T cell homeostasis, were comparable in the spleens of MHCII-/- and WT mice. We have not found the different expression levels of cytokines, chemokines, and growth factors in the serum of MHCII-/- and WT mice so far. However, microarray analysis of genes expressed by transferred CD8 T cells in MHCII-/- and WT mice displayed 77 different expression levels of genes. We are currently attemptingto uncover the function of these candidate genes in memory CD8 T cell maintenance.
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