Control of influenza infection is impaired by diminished interferon‐γ secretion by CD4 T cells in the lungs of toddler mice

Diminished IFN‐γ in the lungs of 21‐ day‐young (toddler) mice throughout infection corresponds to intrinsic rather than extrinsic CD4 T cell limitations in IFN‐γ transcription, indicating a limited CD4 T cell response in toddler age. Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8–10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus, modeling the higher morbidity observed in children (