Developmental Expression of IL-12Rβ2 on Murine Naïve Neonatal T Cells Counters the Up-Regulation of IL-13Rα1 on Primary Th1 Cells and Balances Immunity in the Newborn

摘要

Upon exposure to Ag on the day of birth, neonatal mice mount balanced primary Th1 and Th2 responses with the former displaying up-regulated IL-13 receptor alpha 1 (IL-13Rα1) expression. This chain associates with IL-4Rα to form a heteroreceptor (IL-4Rα/IL-13Rα1) that marks the Th1 cells for death by IL-4 produced by Th2 cells during re-challenge with Ag, hence, the Th2 bias of murine neonatal immunity. The up-regulation of IL-13Rα1 on neonatal Th1 cells was due to the paucity of IL-12 in the neonatal environment. Herein, we show that by day 8 after birth, naïve splenic T cells are no longer susceptible to IL-13Rα1 up-regulation even when exposed to Ag within the neonatal environment. Furthermore, during the 8-day lapse, the naïve splenic T cells spontaneously and progressively up-regulate the IL-12Rβ2 chain, perhaps due to colonization by commensals which induce production of IL-12 by cells of the innate immune system such as dendritic cells. In fact, mature T cells from the thymus, a sterile environment not accessible to microbes, did not up-regulate IL-12Rβ2 and were unable to counter IL-13Rα1 up-regulation. Finally, the 8 day naïve T cells were able to differentiate into Th1 cells even independently of IL-12 but required the cytokine to counter up-regulation of IL-13Rα1. Thus, in neonatal mice, IL-12, which accumulates in the environment progressively, utilizes IL-12Rβ2 to counter IL-13Rα1 expression in addition to promoting Th1 differentiation.