Development for effective induction of memory CD8 T cell against influenza virus.

Research Project

Project/Area Number	18K08456
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54030:Infectious disease medicine-related
Research Institution	International University of Health and Welfare (2019-2021) Institute of Physical and Chemical Research (2018)
Principal Investigator	Yoshizawa Akihiro 国際医療福祉大学, 医学部, 講師 (30407093)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	インフルエンザ / CD8 T細胞 / 免疫記憶 / T細胞 / メモリー / 抑制性分子 / CD8T細胞
Outline of Final Research Achievements	During the cellular adaptive immune response, CD8 T lymphocytes play a central role in mediating protection against myriad infectious pathogens. To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (TR) differentiation, polyclonal responses were compared against NP366-374/Db and PA224-233/Db, two immunodominant epitopes that arise during influenza A infection in mice. We investigate 1) the memory niche where influenza-antigen specific memory CD8 T cells are generated, 2) the micro-enviroment which gives the interaction with other type of cells and 3) the adhesion molecules on the CD8 T cell which foster the persistance within the airway epithelium.
Academic Significance and Societal Importance of the Research Achievements	我々はメモリーCD8 T細胞が形成される“場”のモデルを提唱した。血管と細気管支に近接した粘膜固有層（従来のiBALTとは異なる部位）において、血流を介してCD8 T細胞が集簇する。そこでは、肺マクロファージがTGF-βやIL-15を発現し、一方CD11c陽性樹状細胞がIL-15受容体αを介して、CD8 T細胞にメモリー形質を与える。そして、いくつかは、気道上皮間に移動し、接着分子を介して局在し、次の感染に備えて残留する。こういった、免疫記憶を成立させる微小環境の解明の一端は、今後のウイルスパンデミックに大いに役立つものと考えられる。