2013 Fiscal Year Final Research Report
Role of positive selection in the functional development of T cells
| Project/Area Number |
24790475
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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 | The University of Tokushima |
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Principal Investigator |
TAKADA Kensuke 徳島大学, 疾患プロテオゲノム研究センター, 講師 (40570073)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 獲得免疫 / T細胞 / 正の選択 / 胸腺 |
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| Research Abstract |
beta5t-containing thymoproteasomes expressed in cortical thymic epithelial cells (cTECs) are essential for positive selection of CD8 T cells. In this study, we characterized monoclonal CD8 T cells that were selected in the absence of beta5t. We found that OT-I CD8 T cells generated in beta5t-deficient mice were hyperresponsive to SIINFEKL antigen and its variants. In the periphery, CD8 T cells generated in beta5t-deficient mice were enriched with CD44hiCD122hi memory-phenotype depending on IL-2/15 receptor signals, suggesting that beta5t-dependent positive selection is required for homeostatic maintenance of CD8 T cells. In response to infection with Listeria monocytogenes expressing ovalbumin, OT-I CD8 T cells from beta5t-deficient mice preferentially differentiated into short-lived effector cells. These results indicate that the positive selection in the thymus not only determines TCR recognition specificity but also preconditions antigen responsiveness of CD8 T cells.
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