Stepwise differentiation of follicular helper T cells reveals distinct developmental and functional states.

Follicular helper T (Tfh) cells are essential for the formation of high affinity antibodies after vaccination or infection. Although the signals responsible for initiating Tfh differentiation from naïve T cells have been studied, the signals controlling sequential developmental stages culminating in optimal effector function are not well understood. Here we use fate mapping strategies for the cytokine IL-21 to uncover sequential developmental stages of Tfh differentiation including a progenitor-like stage, a fully developed effector stage and a post-effector Tfh stage that maintains transcriptional and epigenetic features without IL-21 production. We find that progression through these stages are controlled intrinsically by the transcription factor FoxP1 and extrinsically by follicular regulatory T cells. Through selective deletion of Tfh stages, we show that these cells control antibody dynamics during distinct stages of the germinal center reaction in response to a SARS-CoV-2 vaccine. Together, these studies demonstrate the sequential phases of Tfh development and how they promote humoral immunity. © 2023. The Author(s).

Citation

Manuel A Podestà, Cecilia B Cavazzoni, Benjamin L Hanson, Elsa D Bechu, Garyfallia Ralli, Rachel L Clement, Hengcheng Zhang, Pragya Chandrakar, Jeong-Mi Lee, Tamara Reyes-Robles, Reza Abdi, Alos Diallo, Debattama R Sen, Peter T Sage. Stepwise differentiation of follicular helper T cells reveals distinct developmental and functional states. Nature communications. 2023 Nov 24;14(1):7712

Mesh Tags

Substances

PMID: 38001088

search → result