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

## TL;DR

This study reveals that Vγ1+ γδ T cells produce IL-4, which helps activate CD8+ T cells and dendritic cells during malaria infection in mice.

## Contribution

The study identifies a novel role for Vγ1+ γδ T cells in initiating CD8+ T cell immunity through IL-4 production.

## Key findings

- Vγ1+ γδ T cells directly supply IL-4 to initiate CD8+ T cell and dendritic cell responses.
- IL-4 and IFNγ, along with CD40L, synergistically induce IL-12 production by cDC1.
- IL-12 and IL-4 directly signal CD8+ T cells to enhance their expansion and receptor expression.

## 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+ 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.

The authors show how Vγ1+ γδ T cells produce IL-4 to drive early CD8+ T cell and dendritic cell responses to malaria infection in mice.