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bioRxiv · 10.1101/2025.09.08.674857

Requirements for development of T-helper1 and T-follicular helper cells from a common precursor

Bosma, D. M. T.·Busselaar, J.·Staal, M. D.·de Koning, M.·Lei, X.·de Wit, T.·Xiao, Y.·Borst, J.·Salerno, F.
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Abstract

Activated CD4 T cells become either T-helper (Th) or T-follicular helper (Tfh) cells that support cellular or humoral immunity. We have investigated how polyclonal, vaccine induced T cells in mice bifurcate into Th1- and Tfh trajectories. We show that Th1 and Tfh cells originate from the same, highly proliferative precursor clones that co-express Th1- and Tfh-related transcription factors and chemokine receptors, including T-bet, BCL6, CXCR3 and CXCR5. Generation of the common Th1/Tfh precursor pool from antigen-specific CD4 T cells relies on CD28 costimulation but occurs independently of type-1 conventional dendritic cells (cDC1s) or B cells. Differentiation of Th1/Tfh precursors into the Th1 lineage relies on CD40 costimulation and cDC1s, while differentiation into the Tfh lineage relies on ICOS costimulation and B cells. Thus, activated CD4 T cells give rise to a bipotent Th1/Tfh precursor and differentiation into Th1 or Tfh cells depends on interactions with antigen-presenting cDC1s or B cells.

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Bosma, D. M. T., Busselaar, J., Staal, M. D., de Koning, M., Lei, X., de Wit, T., Xiao, Y., Borst, J., Salerno, F.. 2025-09-12. Requirements for development of T-helper1 and T-follicular helper cells from a common precursor. https://doi.org/10.1101/2025.09.08.674857

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