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Background. Despite the high rate of respiratory syncytial virus (RSV) infection and severe symptoms in infants, subsequent infections occur, indicating impaired mucosal immune memory at early life. CD8 T cells are associated with reduced disease in human adult challenge trials and murine models, demonstrating their protective roles. However, since primary RSV infection occurs in infancy, a better understanding of the memory differentiation of RSVspecific respiratory CD8 T cells in neonates is required. Methods. CB6F1/J mice were infected at 7, 14, 25 days of life or adulthood to characterize the RSV-specific memory T-cell development. Cells from mediastinal lymph nodes (MLN) and lungs were analyzed by flow cytometry at 7, 11, 14, and 40 days post RSV infection (dpi) after staining with fluorescent antibodies and tetramers specific for M and M2 epitopes in RSV. Results. RSV-specific CD8 T cell responses were overall lower in neonates from peak to memory phase, but differ by epitope. At 40dpi, M-specific CD8 T cells preferentially differentiated to central-memory (CM) and resided in the MLN in both adult and neonatal mice, whereas M2-specific CD8 T cells preferentially differentiated to effector-memory (EM) and resided in the lungs in adult but not neonatal mice. Importantly, lung tissue resident memory cell differentiation was limited in early life and increased with age upon infection. Conclusion. Our results indicate that the magnitude and memory development of RSV epitope-specific CD8 T cells differ by tissue and age at infection, suggesting that ageassociated mucosal immune factors contribute to the development of RSV-specific memory T cells. ; Age upon RSV infection and epitope-specificity influence the memory differentiation of antiviral T cells Zhongyan Lu1,2, Mathilde Turfkruyer-Husson1,2, Jarina Pena DaMata1,2, Paula Nhan1,2, and Allison M.W. Malloy1 1Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 2Henry M. Jackson Foundation for the Advancement of ... |