Impaired thymopoiesis in interleukin-7 receptor transgenic mice is not corrected by Bcl-2

Abstract

Murine thymocytes down-regulate IL-7 responsiveness following β-selection and reacquire sensitivity after positive selection. To assess the potential consequences of IL-7 signaling during this phase of development, transgenic IL-7 receptor alpha (IL-7Rα) mice were evaluated for IL-7 responsiveness as gauged by STAT-5 phosphorylation. Transgenic IL-7Rα expression increased the percentage of thymocytes responsive to IL-7 yet resulted in a decrease in total thymic cellularity. Aberrant thymocyte development in transgenic mice was first manifested by a reduction of DN3 thymocytes that correlated with lower Bcl-2 expression. Surprisingly, transgenic restoration of Bcl-2 expression did not correct thymic hypocellularity induced by IL-7Rα overexpression. These findings demonstrate that failure to appropriately downregulate IL-7Rα expression interferes with thymocyte development past the pro-T stage resulting in significantly lower levels of mature thymocytes.