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IL-2 Shapes the Survival and Plasticity of IL-17-Producing gammadelta T Cells

Abstract

IL-17-producing gammadelta T (gammadeltaT-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 gammadeltaT-17 cells prompted us to investigate a role for this cytokine. We found gammadeltaT-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 gammadeltaT-17 cells was able to moderate IL-17 and affect differentiation into polyfunctional cytokine-producing cells. Interestingly, the Vgamma6+ subset was more susceptible to the effects of IL-2 than Vgamma4+ gammadeltaT-17 cells. We also found that unlike other gammadelta T cells, gammadeltaT-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 gammadeltaT-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 gammadeltaT-17 response in favor of short-lived effectors with limited plasticity, particularly in the presence of IL-1beta and IL-23. In this way, IL-2 may act to curtail the innate-like response of gammadeltaT-17 cells upon arrival of IL-2-producing adaptive immune cells at the site of inflammation.

Type Journal
ISBN 1550-6606 (Electronic) 0022-1767 (Linking)
Authors Corpuz, T. M.; Vazquez-Lombardi, R.; Luong, J. K.; Warren, J.; Stolp, J.; Christ, D.; King, C.; Brink, R.; Sprent, J.; Webster, K. E.
Responsible Garvan Author Dr Kylie Webster
Publisher Name JOURNAL OF IMMUNOLOGY
Published Date 2017-10-01
Published Volume 199
Published Issue 7
Published Pages 2366-2376
Status Published in-print
DOI 10.4049/jimmunol.1700335
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28835458