IL-2 Shapes the Survival and Plasticity of IL-17-Producing {gamma}{delta} T Cells [IMMUNE REGULATION]

IL-17–producing T (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 T-17 cells prompted us to investigate a role for this cytokine. We found 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-⁺ double producers. Furthermore, the addition of IL-2 to in vitro cultures of sorted T-17 cells was able to moderate IL-17 and affect differentiation into polyfunctional cytokine-producing cells. Interestingly, the V6⁺ subset was more susceptible to the effects of IL-2 than V4⁺ T-17 cells. We also found that unlike other T cells, 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 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 T-17 response in favor of short-lived effectors with limited plasticity, particularly in the presence of IL-1β and IL-23. In this way, IL-2 may act to curtail the innate-like response of T-17 cells upon arrival of IL-2–producing adaptive immune cells at the site of inflammation.

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