Interleukin-15 receptor α signaling constrains the development of IL-17-producing γδ T cells (HEM2P.232)

• Published in: The Journal of immunology (1950) 2015-05, Vol.194 (1_Supplement), p.51-51.2
• Main Authors: Colpitts, Sara, Puddington, Lynn, Lefrançois, Leo
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.194.Supp.51.2

The development and homeostasis of γδ T cells is highly dependent on distinct cytokine networks. Here we examine the role of interleukin (IL)-15 and its unique receptor, IL-15Rα, in the development of IL-17-producing γδ (γδ-17) T cells. Phenotypic analysis showed that CD44high γδ-17 cells expressed IL-15Rα and the common gamma chain (CD132) yet lacked the IL-2/15Rβ chain (CD122). Surprisingly, we found an enlarged population of γδ-17 cells in the peripheral and mesenteric lymph nodes of adult IL-15Rα KO mice but not IL-15 KO mice. γδ-17 cells were also increased in the peripheral lymph nodes of transgenic knock-in mice where the IL-15Rα intracellular signaling domain was replaced with the intracellular portion of the IL-2Rα chain (that lacks signaling capacity). The generation of mixed chimeras from neonatal thymocytes indicated that cell-intrinsic IL-15Rα expression was required to limit IL-17 production by γδ T cells. Finally, an analysis of neonatal thymi revealed that the CD44low precursors of γδ-17 cells were increased in newborn mice lacking IL-15Rα. Thus, these findings demonstrate that signaling through IL-15Rα regulates the development of γδ-17 cells early in ontogeny with long-term effects on their peripheral homeostasis in the adult.