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Stepwise differentiation of follicular helper T cells reveals distinct developmental and functional states
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2023-11-01 |
Deskripsi
Abstract 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.