| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
It has been suggested that memory T follicular helper (Tfh) cells are generated and contribute to a secondary humoral response. Thus, to clarify the mechanisms for generation of memory Tfh cells is relevant for effective vaccine design. Here we demonstrate that Notch signaling regulates generation of memory Tfh cells. During contraction phase, up-regulation of CCR7 and down-regulation of CXCR5 brings Tfh cells into the T-B border area, where they are maintained as memory cells. Lack of Notch signaling during initial antigen priming, but not at the contraction phase, led to a failure of memory T cell generation due to abnormal migration caused by defective CCR7 up-regulation. Notch signaling regulated CCR7 expression through suppression of Blimp-1 expression. Our findings indicate that Notch signaling is critical for the generation and function of memory Tfh cells and could be a future target for the vaccination strategy.
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