Virus-specific airway resident memory CD4 T cell activation accelerates regional priming and accumulation in the lungs of newly primed T cells after Influenza virus challenge 3098

Abstract Description During influenza A virus (IAV) infection, activation of lung tissue resident memory CD4 T cells (TRM) reduce viral titers by boosting local innate inflammation before circulating pathogen-specific T cells arrive. However, optimal clearance of IAV can require responses from both TRM and antiviral T cells primed in secondary lymphoid organs. Whether antigen-sensing by virus-specific TRM can influence the activation of newly primed virus-specific T cells is unknown. To address this, a physiological number of ovalbumin (OVA)-specific lung TRM primed by infecting mice with an IAV strain expressing an MHC II-restricted OVA peptide, were transferred to the airways of naïve host mice. Host mice were then intranasally challenged with a FITC-labelled OVA protein to facilitate tracking of antigen-loaded dendritic cell (DC) migration. We observed faster activation of antigen-bearing (FITC+) DCs in the lung and their more rapid migration to draining lymph nodes (dLN) in mice harboring TRM. Unexpectedly, DC migration was unaffected by CD40 ligand blockade but increased with IFNγ neutralization. TRM-mediated enhanced DC migration led to more rapid accumulation of newly primed OVA-specific CD4 and CD8 T cells in the lungs. Finally, TRM activation also accelerated naive T cell responses during IAV infection. These findings identify a novel aspect of TRM function that accelerates regional priming and accumulation of newly activated T cells in the lung, even amid infection-induced inflammation. Funding Sources Supported by NIH grants R21AI148882 and R01AI167994 (to K.K.M), by a University of Central Florida Doctoral Support Award (to C.M.F.), and by a Solomon Klotz Excellence in Immunology and Allergy Award (to C.M.F.). Topic Categories Mucosal and Regional Immunology (MUC)