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Differential Responsiveness of Innate-like IL-17- and IFN-gamma-Producing gammadelta T Cells to Homeostatic Cytokines

Abstract

gammadelta T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing gammadelta T (gammadeltaT-17) and IFN-gamma-producing gammadelta T (gammadeltaT-IFNgamma) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional gammadelta T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like gammadeltaT-17 and gammadeltaT-IFNgamma cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional gammadelta T cells, but they do not monopolize the same cytokine. gammadeltaT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. gammadeltaT-IFNgamma cells instead depend heavily on IL-15. They display traits analogous to memory CD8(+) T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional gammadelta T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive alphabeta T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that gammadelta T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes.

Type Journal
ISBN 1550-6606 (Electronic) 0022-1767 (Linking)
Authors Corpuz, T. M.; Stolp, J.; Kim, H. O.; Pinget, G. V.; Gray, D. H.; Cho, J. H.; Sprent, J.; Webster, K. E.;
Publisher Name J IMMUNOL
Published Date 2016-01-01 00:00:00
Published Volume 196
Published Issue 2
Published Pages 645-54
URL http://www.ncbi.nlm.nih.gov/pubmed/26673141
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?13775_13543/2016-Corpuz-J Immunol.pdf