Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 13, Issue 2, Pages 217-228Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cmi.2015.07
Keywords
cytokines; signal transduction; T-cell receptors; T cells; tumor immunity
Categories
Funding
- Research Special Fund for Public Welfare Industry of Health [201202004, 201302018]
- National Program for Key Basic Research Projects, Ministry of Science and Technology, China [2013CB530503, 2014CB542103]
- Beijing Natural Science Foundation [5122031]
- National Natural Science Foundation of China [30972776]
- National High Technology Research and Development Program (863 Program) [2007AA021109]
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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 (gamma delta) T cells remains unclear. In this study, we investigate the effects of IL-4 on the activation and proliferation of gamma delta T cells and the balance between variable delta 1 (V delta 1) and V delta 2 T cells in humans. The results show that IL-4 inhibits the activation of cd T cells in the presence of gamma delta T-cell receptor (TCR) stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated cd T cells and increased the levels of V delta 1 T cells, which in turn inhibited V delta 2 T-cell growth via significant IL-10 secretion. V delta 1 T cells secreted significantly less interferon gamma (IFN gamma) and more IL-10 relative to V delta 2. Furthermore, V delta 1 T cells showed relatively low levels of Natural Killer Group 2D (NKG2D) expression in the presence of IL-4, suggesting that V delta 1 T cells weaken the gamma delta T cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in gamma delta T cell-mediated anti-tumor immunity.
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