Elucidation of mechanism of memory Tfh cell generation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokyo University of Science
• Principal Investigator: Harada Yohsuke 東京理科大学, 薬学部生命創薬科学科, 講師 (20328579)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: T細胞 / B細胞 / 抗体 / 免疫記憶 / 液性免疫

Outline of Final Research Achievements

Although Tfh cells are crucial for the humoral immune response, there are no tools to track the fate of Tfh cells. In this study, we generated two reporter mice that enables Tfh cell tracking in vivo. Using these reporter mice, we demonstrated that Tfh cells could be tracked from the effector phase to the memory phase. During the contraction phase, the localization of Tfh cells changed from B cell follicles and GC areas to T-B border areas and T cell zones. These results indicate that these mice are useful tools for studying the cell fate of differentiated Tfh cells in vivo and therefore have implications for the development of therapeutic strategies for infectious and autoimmune diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまでTfh細胞特異的な遺伝子改変が可能なツールは報告されていなかったが、今回我々が作製したCxcr5CreERT2マウスとBcl6Tomato-CreERT2マウスは、それを可能とする世界初のツールである。これらのマウスを使うことで、生体内でTfh細胞を継続的に追跡することが可能になった。これらのマウスの解析からTfh細胞のメモリー細胞への分化やTfh由来メモリー細胞の維持のメカニズムが明らかになれば、新たなワクチンやアレルギー、自己免疫疾患の治療薬の開発につながるだろう。