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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1481243
This article is part of the Research Topic Follicular Helper T Cells in Immunity and Autoimmunity - Volume II View all 5 articles

TCR-CD3 signal strength regulates plastic coexpression of IL-4 and IFN-γ in Tfh-like cells

Provisionally accepted
Niels Verstegen Niels Verstegen 1*Tineke Jorritsma Tineke Jorritsma 1Anja t. Brinke Anja t. Brinke 1Matteo Barberis Matteo Barberis 2S. Marieke Van Ham S. Marieke Van Ham 1
  • 1 Sanquin Research, Amsterdam, Netherlands
  • 2 University of Surrey, Guildford, South East England, United Kingdom

The final, formatted version of the article will be published soon.

    The development of T follicular helper (Tfh) cells is an ongoing process resulting in the formation of various Tfh subsets. Despite advancements, the precise impact of T cell receptor (TCR) stimulation on this process remains incompletely understood. This study explores how TCR-CD3 signaling strength influences naive CD4 + T cell differentiation into Tfh-like cells and the concurrent expression of interleukin-21 (IL-21), interleukin-4 (IL-4), and interferon-gamma (IFN-γ). Strong TCR-CD3 stimulation induces proliferation and increased IL-21 expression in Tfh-like cells, which exhibit a characteristic phenotype expressing CXCR5 and PD1. The coexpression of IL-4 and IFN-γ in IL-21producing Tfh-like cells is controlled by the strength TCR-CD3 stimulation; low stimulation favors IL-4, while strong stimulation enhances IFN-γ secretion. Exogenous addition of the effector cytokines IL-21 and IL-4 further modulate cytokine coexpression. These findings highlight the intricate regulatory mechanisms governing cytokine production and plasticity in Tfh-like cells, providing insights into B cell response modulation. In vivo, antigen availability may regulate Tfh cell plasticity, impacting subsequent B cell differentiation, emphasizing the need for further exploration through animal models or antigen-specific Tfh cell analyses in human lymph node biopsies.

    Keywords: TCR signaling, Tfh cell, cytokine plasticity, IL-21, T cell diferentiation

    Received: 15 Aug 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Verstegen, Jorritsma, Brinke, Barberis and Van Ham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Niels Verstegen, Sanquin Research, Amsterdam, Netherlands

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.