IL-2 Shapes the Survival and Plasticity of IL-17–Producing γδ T Cells
JOURNAL OF IMMUNOLOGY(2017)
Abstract
IL-17 producing gamma delta T (gamma delta T-17) cells have proved to be an important early source of IL-17 in many inflammatory settings and are emerging as an important participant in protumor immune responses. Considering that their peripheral activation depends largely on innate signals rather than TCR ligation, it is important to understand what mechanisms exist to curb unwanted activation. Expression of the high-affinity IL-2R on gamma delta T-17 cells prompted us to investigate a role for this cytokine. We found gamma delta T-17 cells to be enriched, not depleted, in IL-2 deficient mice. The absence of IL-2 also resulted in higher IL-17 production and the emergence of IL-17(+)IFN-gamma(+) double producers. Furthermore, the addition of IL-2 to in vitro cultures of sorted gamma delta T-17 cells was able to moderate IL-17 and affect differentiation into polyfunctional cytokine-producing cells. Interestingly, the V gamma 6(+) subset was more susceptible to the effects of IL-2 than V gamma 4(+) gamma delta T-17 cells. We also found that unlike other gamma delta T cells, gamma delta T-17 cells do not produce IL-2, but express Blimp-1, a known transcriptional repressor of IL-2. Although IL-2 was able to induce robust proliferation of gamma delta T-17 cells, it did not sustain viability, negatively impacting their survival via downregulation of the IL-7R. Taken together, these data indicate that IL-2 can augment the gamma delta T-17 response in favor of short-lived effectors with limited plasticity, particularly in the presence of IL-1 beta and IL-23. In this way, IL-2 may act to curtail the innate-like response of gamma delta T-17 cells upon arrival of IL-2 producing adaptive immune cells at the site of inflammation.
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