Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells
Veronica Martini, Matthew Edmans, Simon Gubbins, S. Jayaraman, Basudev Paudyal, Sophie Morgan, Adam McNee, Théo Morin, Pramila Rijal, Wilhelm Gerner, Andrew K. Sewell, Ryo Inoüe, Mick Bailey, Timothy Connelley, Bryan Charleston, Alain Townsend, Peter C. L. Beverley, Elma Tchilian
Abstract
For the first time we have defined naïve, central memory, effector memory and differentiated effector porcine CD8 T cells and analyzed their distribution 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 downregulate CD45RA and CCR7. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. In all tissues the frequency of NP-specific CD8 cells declines over 63 days almost to background levels but is best maintained in BAL. The kinetic of influenza specific memory CD8 T cell in this natural host species differs from that in small animal models.