A role for interleukin-15Rα signaling in the homeostasis of early T cell progenitors (LYM7P.716)

Abstract

Abstract A deficiency in interleukin-15 receptor α (IL-15Rα) expression is associated with an overall decrease in thymic cellularity. To further investigate this defect, we examined T cell progenitors in the thymus of wild-type (WT) and IL-15Rα KO mice. We identified a significant reduction specifically within the subset of CD27high cells in the CD44highCD25- double negative (DN1) population of T cell progenitors in the absence of IL-15Rα. Since T cell development begins early in ontogeny, we also examined the thymus of WT and IL-15Rα KO neonates (<24hrs post-birth). Surprisingly, we found no differences in the total numbers of neothymocytes or CD27high DN1 cells suggesting that the aforementioned deficiencies are acquired over time. Finally, while IL-15Rα functions largely through the transpresentation of IL-15, it also has the capacity to signal directly. To determine which of these two roles might be involved in the long-term homeostasis of thymic progenitors, we used a transgenic mouse strain that expresses a chimeric receptor composed of the extracellular domain of IL-15Rα and the intracellular domain of the IL-2Rα, thus efficiently disrupting IL-15Rα signaling while maintaining transpresentation. We found that, similar to IL-15Rα KO mice, IL-15Rα signaling transgenics also exhibited a significant decrease in the subset of CD27high DN1 cells suggesting that direct signaling through IL-15Rα is required for optimal homeostasis of early T cell progenitors in the thymus.