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

Cellular & Molecular Immunology volume 13, pages 217–228 (2016)Cite this article

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 T 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 T cells in the presence of γδ T-cell receptor (TCR) stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated γδ T 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 T cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in γδ T cell-mediated anti-tumor immunity.

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Acknowledgements

We thank Dr Mingxiao He (Duke University for Immunology Research) for critical reading of this manuscript. This work was supported by the Research Special Fund for Public Welfare Industry of Health (Grant Nos. 201202004 and 201302018), the National Program for Key Basic Research Projects, Ministry of Science and Technology, China (2013CB530503 and 2014CB542103), the Beijing Natural Science Foundation (Grant No. 5122031), the National Natural Science Foundation of China (Grant No. 30972776) and the National High Technology Research and Development Program (863 Program) (Grant No. 2007AA021109). We thank Dr Austin Cape for careful reading and feedback.

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Authors and Affiliations

  1. Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China

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

  2. State Key Laboratory of Medical Molecular Biology, Beijing, China

    Jianmin Zhang, Yu Hu, Lianxian Cui, Ning Kang & Wei He

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  1. Yujia Mao
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Mao, Y., Yin, S., Zhang, J. et al. A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells. Cell Mol Immunol 13, 217–228 (2016). https://doi.org/10.1038/cmi.2015.07

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