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

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.