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

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<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 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.

Authors

Institutions

Publication Details

Journal
Nature Immunology
Published
2026-01-30
DOI
https://doi.org/10.1038/s41590-025-02397-z
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Luke C. Gandolfo, Zhengyu Ge, Calvin Xu, Ian A. Cockburn et al.
Nature Immunology
T-cell and B-cell Immunology
article

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

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

Abstract

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<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 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.

Nature ImmunologyVol. 27(2)
Australian National University (AU), Burnet Institute (AU), The University of Melbourne (AU), La Trobe University (AU), UNSW Sydney (AU), Melbourne Bioinformatics (AU), Menzies School of Health Research (AU), Peter Doherty Institute (AU), Monash University (AU)
Openalex Percentile: Top 72%
T-cell and B-cell Immunology
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.