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

Upon exposure to Ag on the day of birth, neonatal mice mount balanced primary Th1 and Th2 responses, with the former displaying upregulated IL-13R alpha 1 expression. This chain associates with IL-4R alpha to form a heteroreceptor (IL-4R alpha/IL-13R alpha 1) that marks the Th1 cells for death by IL-4 produced by Th2 cells during rechallenge with Ag, hence the Th2 bias of murine neonatal immunity. The upregulation of IL-13R alpha 1 on neonatal Th1 cells was due to the paucity of IL-12 in the neonatal environment. In this study, we show that by day 8 after birth, naive splenic T cells are no longer susceptible to IL-13R alpha 1 upregulation even when exposed to Ag within the neonatal environment. Furthermore, during the 8-d lapse, the naive splenic T cells spontaneously and progressively upregulate the IL-12R beta 2 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 upregulate IL-12R beta 2 and were unable to counter IL-13R alpha 1 upregulation. Finally, the 8-d naive T cells were able to differentiate into Th1 cells even independently of IL-12 but required the cytokine to counter upregulation of IL-13R alpha 1. Thus, in neonatal mice, IL-12, which accumulates in the environment progressively, uses IL-12R beta 2 to counter IL-13R alpha 1 expression in addition to promoting Th1 differentiation.