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<p>Dendritic cells (DCs) are pivotal for initiating adaptive immunity, a process triggered by the activation of DCs via pathogen products or damage. Immunization with sporozoites from <i>Plasmodium</i> leads to CD8<sup>+</sup> T cell priming in a response initiated by collaboration between conventional type 1 DCs (cDC1s) and γδ T cells. Here we show that Vγ1<sup>+</sup> γδ T cells have an initiating role by directly supplying interleukin-4 (IL-4). IL-4 and interferon-γ (IFNγ) synergize with CD4<sup>+</sup> T cell-derived CD40L to induce IL-12 production by cDC1. Both IL-12 and IL-4 then directly signal responding CD8<sup>+</sup> T cells and drive enhanced IL-12 receptor expression and expansion. This study shows how Vγ1<sup>+</sup> γδ T cells can initiate CD8<sup>+</sup> T cell immunity to <i>Plasmodium</i> and that responses to some pathogens require help from innate-like T cells to pass an initiation threshold and further amplify the response in a process underscored by IL-4 production.</p>

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γδ T cell-derived IL-4 initiates CD8+ T cell immunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • Shirley Le,
  • Nick Dooley,
  • Declan Murphy,
  • Shangyi Liu,
  • Luke C. Gandolfo,
  • Zhengyu Ge,
  • Rose May,
  • Anton Cozijnsen,
  • Thomas N. Burn,
  • Charlie Jennison,
  • Annabell Bachem,
  • Calvin Xu,
  • Hui-Fern Koay,
  • Jan Schröder,
  • Damian Oyong,
  • Mayimuna Nalubega,
  • Enny Kenangalem,
  • Stephanie Gras,
  • Ian A. Cockburn,
  • Sammy Bedoui,
  • Laura K. Mackay,
  • Geoffrey I. McFadden,
  • Daniel Fernandez-Ruiz,
  • Michelle Boyle,
  • William R. Heath,
  • Lynette Beattie

摘要

Dendritic cells (DCs) are pivotal for initiating adaptive immunity, a process triggered by the activation of DCs via pathogen products or damage. Immunization with sporozoites from Plasmodium leads to CD8+ T cell priming in a response initiated by collaboration between conventional type 1 DCs (cDC1s) and γδ T cells. Here we show that Vγ1+ γδ T cells have an initiating role by directly supplying interleukin-4 (IL-4). IL-4 and interferon-γ (IFNγ) synergize with CD4+ T cell-derived CD40L to induce IL-12 production by cDC1. Both IL-12 and IL-4 then directly signal responding CD8+ T cells and drive enhanced IL-12 receptor expression and expansion. This study shows how Vγ1+ γδ T cells can initiate CD8+ T cell immunity to Plasmodium and that responses to some pathogens require help from innate-like T cells to pass an initiation threshold and further amplify the response in a process underscored by IL-4 production.