Neonatal mice possess two phenotypically and functionally distinct lung-migratory CD103⁺ dendritic cell populations...

The CD103⁺ subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8⁺ T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103⁺ DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103⁺ DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103⁺ DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited. CD103lo DCs sorted from infected neonates were unable to stimulate cells of the K^dM2_82-90 specificity, which are potently stimulated by CD103hi DCs sorted from the same animals. These data suggest that the delayed maturation of CD103⁺ DCs in the neonate limits the K^dM2_82-90-specific response and explain the distinct CD8⁺ T cell response hierarchy displayed in neonatal mice that differs from the hierarchy seen in adult mice. These findings have implications for the development of early-life vaccines, where the promotion of responses with less age bias may prove advantageous. Alternately, specific approaches may be used to enhance the maturation and function of the CD103lo DC population in neonates to promote more adult-like T cell responses.