Developmental queues dictate IL-15 expression in γδ T cells (115.4)

Abstract

Abstract Interleukin-15 (IL-15) is a homeostatic cytokine largely produced by myeloid cells. Surprisingly, analysis of a recently generated transgenic reporter mouse using emerald GFP expression as a surrogate for IL-15 promoter activity (EmGFP/IL-15) revealed unexpected expression in lymphoid γδ T cells. Similar to myeloid cells, in which EmGFP/IL-15 is developmentally regulated in the bone marrow, we found that EmGFP/IL-15 expression was downregulated as EmGFP/IL-15high thymic progenitors committed to a mature T cell fate. EmGFP/IL-15 was significantly reduced between DN2 and DN3 cells and silenced in DN4 and single positive thymocytes. However, γδ T cells and their precursors (CD25+ pre-γδ T cells) maintained low levels of EmGFP/IL-15, which was similar to DN3 cells. Interestingly, we found that intestinal intraepithelial γδ T cells were EmGFP/IL-15neg while a small subset of γδ T cells located in the peripheral lymph nodes expressed elevated levels of EmGFP/IL-15. These cells had a CD44highCD62LlowCD27lowCCR6+ phenotype, which corresponded to the Vγ2+ subset of IL-17-producing γδ T cells. These findings suggest that EmGFP/IL-15 is regulated concomitantly with the waves of γδ T cell development occurring perinatally and that transcriptional regulation at the IL-15 locus may overlap with that of IL-17-inducing machinery. Current studies aim to determine if the novel production of IL-15 by γδ T cells contributes to the overall homeostasis of IL-15-dependent cells in vivo.