Age-Dependent Differences in T-Cell Responses to Influenza A Virus

Respiratory infections from influenza A virus (IAV) cause substantial morbidity and mortality in children relative to adults. T cells play a critical role in the host response to IAV by supporting the innate and humoral responses, mediating cytotoxic activity, and promoting recovery. There are age-dependent differences in the number, subsets, and localization of T cells, which impact the host response to pathogens. In this article, we first review how T cells recognize IAV and examine differences in the resting T-cell populations between juveniles and adults. Next, we describe how the juvenile CD4⁺, CD8⁺, and regulatory T-cell responses compare with those in adults and discuss the potential physiologic and clinical consequences of the differences. Finally, we explore the roles of two unconventional T-cell types in the juvenile response to influenza, natural-killer T cells and γδ T cells. A clear understanding of age-dependent differences in the T-cell response is essential to developing therapies to prevent or reverse the deleterious effects of IAV in children.