Tissue resident memory T cell responses to RSV infection are reduced in infant mice compared to adults

Abstract

Abstract Tissue resident memory T cells (TRMs) are an important yet incompletely understood cell population that enhance the clearance of respiratory syncytial virus (RSV) infection in both humans and animal models of disease. Limited data in an influenza model of disease suggests the establishment of TRMs in infants is impaired, but the establishment of TRMs during infant RSV infection is unknown. The purpose of this study was to characterize the quantity and function of infant TRM responses to RSV infection. To address this, BALB/c mice were infected with RSV as 10-day old mice or as 6–8-week-old adults. Peripheral T cells were then depleted using FTY720 at the time of an RSV re-challenge 4–5 weeks later. TRM response was evaluated using flow cytometry; viral titers and histological staining were used to assess disease outcomes. Mice infected as infants had significantly lower total numbers of CD4+ and CD8+ TRMs compared to those infected as adults. Furthermore, TRMs established in infancy showed a Th2-biased response, with increased production of IL-4 and IL-10 compared to adults, while adult TRMs produced more granzyme B from CD8+ cells and increased IFNγ from both CD4+ and CD8+ T cells. Mice infected in infancy also showed increased %PAS positive airways compared to those infected initially as adults, suggesting more severe RSV disease. In conclusion, infants have reduced ability to establish TRMs following RSV infection and their TRM population exhibits Th2 skewing. Further studies are needed to elucidate the mechanisms that prevent effective establishment of TRMs following infant pulmonary infections.