Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells

Martini, Veronica; Edmans, Matthew; Gubbins, Simon; Jayaraman, Siddharth; Paudyal, Basu; Morgan, Sophie; McNee, Adam; Morin, Théo; Rijal, Pramila; Gerner, Wilhelm; Sewell, Andrew K.; Inoue, Ryo; Bailey, Mick; Connelley, Timothy; Charleston, Bryan; Townsend, Alain; Beverley, Peter; Tchilian, Elma

We defined naïve, central memory, effector memory and terminally differentiated porcine CD8 T cells and analyzed their phenotype in lymphoid and respiratory tissues after influenza infection or immunization using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM), that express CD69 and have an effector memory or terminally differentiated phenotype. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. The frequency of NP-specific cells declines over 63 days in all tissues but is best maintained in BAL. The pig is a powerful model for understanding how best to induce and harness local immunity to respiratory viruses. One sentence summary Influenza NP-specific porcine tissue resident memory CD8 T cells persist in the lung with major changes in gene expression.