Immunity in the newborn: control by IL-13 receptor and dendritic cells

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Neonates are susceptible to microbial infections and allergic reactions due to lack of Th1 immunity. Utilization of a TCR transgenic T cell transfer system, we demonstrated that primary neonatal Th1 cells develop alongside Th2 cells 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-13R[alpha]1 chain expression. Our data suggested that IL-4 might use this receptor chain to signal for the apoptosis of Th1 cells leading to lack of Th1 immunity in neonates. The point at which neonates no longer exhibit a Th2 biased immune response has not been studied. Interestingly, we found that antigen exposure at day 6 after birth restored the secondary Th1 response concomitantly with IL-13R[alpha]1 mRNA downregulation. Our data suggest that up-regulation of IL-13R[alpha]1 at day 1 is due to delayed maturation of the CD8[alpha]+CD4- DC subset capable of IL-12 production. CD8[alpha]+CD4- DC subset transfer to 1 day old neonates diminished IL-13R[alpha]1 expression by IL-12 secretion, leading to inhibition of Th1 apoptosis and restoration of an adult-like Th1 immunity.