| Budget Amount *help |
¥129,350,000 (Direct Cost: ¥99,500,000、Indirect Cost: ¥29,850,000)
Fiscal Year 2022: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
Fiscal Year 2021: ¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Fiscal Year 2020: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2019: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
Fiscal Year 2018: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
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| Outline of Final Research Achievements |
First, we demonstrated that autoreactive CD8+ T cells in NOD mice went through four activation phases and PD-1 strongly attenuated the transition from the second to the third phase, where effector functions were acquired by analyzing their activation trajectory. Next, we found that T cell receptor (TCR) signal strength required for the induction of genes varies across different genes and PD-1 preferentially inhibits the induction of genes that require stronger TCR signal. We further demonstrated that PD-1 inhibits the expression of TCR-inducible genes efficiently when the affinity between TCR and peptide-MHC complex is low. These results indicate that inhibitory co-receptors do not weaken T cell responses uniformly, but they impose qualitative control of T cell responses. We also revealed the establishment of immuno-suppressive environment in tumors and draining lymph nodes during the early phase of tumor development, which attenuates the proliferation of tumor-specific T cells.
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