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<p>CD4<sup>+</sup> T follicular helper (T<sub>FH</sub>) cells support tailored B cell responses against multiple classes of pathogens. To reveal how diverse T<sub>FH</sub> phenotypes are established, we profiled mouse T<sub>FH</sub> cells in response to viral, helminth and bacterial infection. We identified a core T<sub>FH</sub> signature that is distinct from CD4<sup>+</sup> T follicular regulatory and effector cells and identified pathogen-specific transcriptional modules that shape T<sub>FH</sub> function. Cytokine-transcriptional T<sub>FH</sub> programming demonstrated that type I interferon and TGFβ signaling direct individual T<sub>FH</sub> phenotypes to instruct B cell output. Cytokine-directed T<sub>FH</sub> transcriptional phenotypes are shared within human germinal centers, but distinct T<sub>FH</sub> phenotypes dominate between donors and following immune challenge or in antibody-mediated disease. Finally, we identified new cell surface markers that align with distinct T<sub>FH</sub> phenotypes. Thus, we provide a comprehensive resource of T<sub>FH</sub> diversity in humans and mice to enable immune monitoring during infection and disease and to inform the development of context-specific vaccines.</p>

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Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月9日

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  • Lennard Dalit,
  • Chin Wee Tan,
  • Amania A. Sheikh,
  • Ryan Munnings,
  • Lauren J. Howson,
  • Carolina Alvarado,
  • Tabinda Hussain,
  • Aidil Zaini,
  • Lucy Cooper,
  • Alana Kirn,
  • Lauren Hailes,
  • Angela Nguyen,
  • Bailey E. Williams,
  • Ming Z. M. Zheng,
  • Carolien E. van de Sandt,
  • Laura K. Mackay,
  • Katie L. Flanagan,
  • Katherine Kedzierska,
  • Nicola Harris,
  • Jennifer A. Juno,
  • Colby Zaph,
  • Nicole L. La Gruta,
  • Melissa J. Davis,
  • Stephen L. Nutt,
  • Kim L. Good-Jacobson,
  • Vanessa L. Bryant,
  • Joanna R. Groom

摘要

CD4+ T follicular helper (TFH) cells support tailored B cell responses against multiple classes of pathogens. To reveal how diverse TFH phenotypes are established, we profiled mouse TFH cells in response to viral, helminth and bacterial infection. We identified a core TFH signature that is distinct from CD4+ T follicular regulatory and effector cells and identified pathogen-specific transcriptional modules that shape TFH function. Cytokine-transcriptional TFH programming demonstrated that type I interferon and TGFβ signaling direct individual TFH phenotypes to instruct B cell output. Cytokine-directed TFH transcriptional phenotypes are shared within human germinal centers, but distinct TFH phenotypes dominate between donors and following immune challenge or in antibody-mediated disease. Finally, we identified new cell surface markers that align with distinct TFH phenotypes. Thus, we provide a comprehensive resource of TFH diversity in humans and mice to enable immune monitoring during infection and disease and to inform the development of context-specific vaccines.