Dendritic cells influence the altered neonatal CD8 T cell immunodominance hierarchy during influenza virus infection

Abstract

Abstract Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality as well as delayed clearance of the virus. Previous work has indicated that decreased T cell and dendritic cell function underlies some of this vulnerability. We sought to understand CD8 T cell specificity and immunodominance during neonatal influenza infection as well as how any differences from the adult hierarchy might impact immunodominance and protection in subsequent infections. We found that neonatal C57BL/6 mice display an altered CD8 T cell immunodominance hierarchy, preferentially responding to an epitope in the influenza protein PA rather than the co-dominant adult response to NP and PA. Additionally, upon secondary infection, mice first infected as pups display inconsistent immunodominance and suffer increased morbidity compared to mice infected previously as adults. Finally, transfer of influenza infected adult dendritic cells to pups resulted in increased T cell activation and enhanced viral clearance as well as a slight induction of NP specific CD8 T cells. Taken together, these data suggest that infection early in life alters the specificity of memory responses to that pathogen and that dendritic cells may play a role in mediating this process. Additionally, vaccines targeting T cells should consider epitope usage and age specific dendritic cell physiology if the intended patient population includes infants as well as adults.