Stepwise regulation of neonatal immunity by IL-4α/IL-13Rα1 HR. During neonatal exposure to Ag, basophils function as APCs and produce IL-4. This cytokine binds to the HR on neighboring Ag presenting DCs and signals malfunction and diminished IL-12 production. Limited IL-12 in the neonatal environment, although sufficient to drive differentiation of naïve T cells into Th1 cells, cannot counter up-regulation of IL-13Rα1. Consequently, HR formation on neonatal Th1 cells ensues and serves as a death marker for the cells. During rechallenge with Ag, Th2 cells produce IL-4 which signals apoptosis of Th1 cells leading to bias of secondary immunity towards Th2 cells. In fact, if the DCs are devoid of the HR, IL-4 from basophils will not be able to limit IL-12 production by DCs. In this case, Th1 differentiation will occur but without HR expression yielding Th1/Th2 balanced neonatal immunity.