IL-4 Utilizes an Alternative Receptor to Drive Apoptosis of Th1 Cells and Skews Neonatal Immunity toward Th2

AbstractPrimary neonatal Th1 cells develop alongside of Th2 upon priming of the newborn but undergo apoptosis upon recall with antigen. These Th1 cells were isolated, and their death was correlated with elevated IL-13Rα1 chain expression. Strikingly, neutralization of Th2s′ IL-4 reduced apoptosis, sustained recall responses, and the live Th1 cells displayed a decrease in IL-13Rα1 expression. Blockade of IL-13Rα1 or IL-4Rα also restores recall and secondary Th1 responses. Adult T cells primed within the neonatal environment did not upregulate IL-13Rα1 chain or undergo apoptosis and developed recall Th1 responses. These observations indicate that developmental expression of IL-13Rα1 along with IL-4Rα provides a receptor through which IL-4 induces death of Th1 cells and skews neonatal immunity toward Th2