A new effect of IL-4 on human γδ cells: Promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells

Yujia Mao, Shanshan Yin, Jianmin Zhang, Yu Hu, Bo Huang, Lianxian Cui, Ning Kang, Wei He

Research output: Contribution to journalArticle

Abstract

Interleukin 4 (IL-4) has a variety of immune functions, including helper T-cell (Th-cell) differentiation and innate immune-response processes. However, the impact of IL-4 on gamma delta (γδ) T cells remains unclear. In this study, we investigate the effects of IL-4 on the activation and proliferation of γδ cells and the balance between variable delta 1 (Vδ1) and Vδ2 T cells in humans. The results show that IL-4 inhibits the activation of γδ cells in the presence of γδ-cell receptor (TCR) stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated γδ cells and increased the levels of Vδ1 T cells, which in turn inhibited Vδ2 T-cell growth via significant IL-10 secretion. Vδ1 T cells secreted significantly less interferon gamma (IFNγ) and more IL-10 relative to Vδ2. Furthermore, Vδ1 T cells showed relatively low levels of Natural Killer Group 2D (NKG2D) expression in the presence of IL-4, suggesting that Vδ1 T cells weaken the γδ cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in γδ cell-mediated anti-tumor immunity.

Original languageEnglish (US)
Pages (from-to)217-228
Number of pages12
JournalCellular and Molecular Immunology
Volume13
Issue number2
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • cytokines
  • signal transduction
  • T cells
  • T-cell receptors
  • tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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