Adult mice with neonatal-like T cell subsets exhibit increased susceptibility to Bordetella pertussis and influenza infection

Abstract

Infants are significantly more susceptible to respiratory infection, often resulting in increased morbidity and hospitalization, and occasionally death. This susceptibility is partially explained by the developing nature of the thymus in human infants at, and for several months after, birth. However, the contribution of T cells produced in this thymic microenvironment to infant immune responses has received minimal investigation. Here, we utilized a previously described mouse model (Foxn1{Delta}/{Delta}) which exhibits a persistently immature thymus. Through further characterization, we have determined that adult Foxn1{Delta}/{Delta} mice retain some unique T cells observed in neonatal mice including CD8{beta}+ {gamma}{delta} T cells and CD8 T cells displaying a memory-like phenotype. For this reason, we assessed the potential of these neonatal-like T responses to two pathogens which disproportionately affect neonates, Bordetella pertussis (Bp) and influenza. Utilizing these infections, we demonstrate that T cells generated in an incompletely developed thymus fail to control or mount an effective response against Bp. We also observe that Foxn1{Delta}/{Delta} mice control acute influenza infection, a response which does not require IL-17. However, the Foxn1{Delta}/{Delta} mice fail to generate an influenza nucleoprotein (NP) specific CD8+ T cell response which is likely associated with their inability to fully clear the infection. Together, these data suggest that Foxn1{Delta}/{Delta} mice can be utilized to study the generation, function, and persistence of some unique T cells made in a neonatal-like thymus.