The protective role of γδ T cells in neonatal influenza (INC1P.348)

Influenza virus infection is a continuing world-wide health threat, especially in infants and the elderly. Neonates are highly susceptible to influenza infection, which is often a cause of hospitalization. γδ T cells are the first T cells to develop during embryogenesis and dominate among the neonatal immune system components, as conventional αβ T cell responses are functionally less prominent. Hence, γδ T cells are poised to play a critical role in neonatal infections; however, the specific role of γδ T cells in neonatal influenza infection remains to be elucidated. Using a neonatal mouse model of intranasal influenza infection, we observed the accumulation of γδ T cells within two days after infection. By utilizing the Nur77-GFP reporter mice, we demonstrated that the activation of these γδ T cells was via the T cell receptor. IL-17-producing γδ T cells, rather than IFN-γ-producing cells, dominated in the primary response. A comparison between wild-type and TCRδ-deficient neonates identified a protective function of γδ T cells in neonates. Reduced weight loss and an increased survival rate were observed in the wild-type compared to TCRδ-deficient animals. In infected lungs, wild-type neonates also had more robust IFN-β production and increased inflammatory cytokine production. Our findings demonstrate a vital role for γδ T cells in mediating protection during neonatal influenza virus infection, which may provide a new therapeutic target for pediatric influenza treatment.