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Sci Immunol ; 9(93): eadd4818, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427718

RESUMO

T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-ß (TGF-ß) induces robust expression of TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-ß-induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated TFH cells and provide critical help to B cells. The study further reveals that TGF-ß-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-ß-containing T helper 17 (TH17)-inducing conditions also yield separate CXCR5+ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-ß-induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-ß-rich environments in vitro and in vivo.


Assuntos
Linfócitos T Auxiliares-Indutores , Fator de Crescimento Transformador beta , Animais , Camundongos , Fator de Crescimento Transformador beta/metabolismo , Linfócitos B , Linfócitos T CD4-Positivos , Diferenciação Celular , Proteínas Proto-Oncogênicas c-maf/metabolismo
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