Elucidation of NK cell activation and retrovirus infection defense mechanism induced by peptide immunization against murine Friend retrovirus

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16622
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kindai University
• Principal Investigator: KATO Shigeki 近畿大学, 医学部, 助教 (90790767)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: レトロウイルス / ワクチン / がん

Outline of Final Research Achievements

We worked on elucidating the host immune response, especially the activation mechanism of NK cells, using a mouse retrovirus and an infection-defensive mouse model. Early activation of NK cells is required for elimination of infected cells, but the specific effector mechanism was unknown. We found in this study that IL-21 expression by antigen-specific follicular helper T cells in the early stage of infection acts on IL-21 R on NK cells to induce maturation and activation of NK cells, which clearly eliminated the infected cells. Furthermore, it was revealed that CD154 on NK cells regulates IL-21 R expression by receiving stimuli from CD40 of dendritic cells and macrophages in the early stage of infection.

Free Research Field

免疫

Academic Significance and Societal Importance of the Research Achievements

本研究は，適切なエピトープ選択による免疫によって早期に Tfh が誘導されることは，NK細胞の活性化をもたらすことにつながりウイルス感染細胞を効率的に排除することが可能であるという新規メカニズムを証明したことを意味し，新たなワクチン開発につながることが期待される．
従来，NK 細胞は抗原感作が不要と考えられてきたが，CD4 陽性 T 細胞を適切なエピトープで免疫すれば NK 細胞に間接的に抗原特異性を賦与できること，また，樹状細胞やマクロファージなどの抗原提示細胞の CD40 分子が効率的な NK 細胞活性化に重要であるという分子基盤を明らかにした．