Influenza-Induced CD103⁺ T Resident Memory Cells Exhibit Enhanced Functional Avidity over CD103^- Memory T Cells in...

Influenza virus-specific tissue-resident memory CD8 T cells (Trms) targeting conserved viral proteins provide strain-transcending heterosubtypic immunity to infection. Trms in the lung combat reinfection through rapid cytolytic function and production of inflammatory cytokines to recruit other immune cells. Influenza-specific Trms are also generated in the lung draining mediastinal lymph node (mLN) and can provide immunity to heterologous virus infection in this tissue, although their role in combating influenza infection is less well defined. Functional avidity, a measure of T cell sensitivity to Ag stimulation, correlates with control of viral infection and may be important for immune detection of recently infected cells, when low numbers of surface peptide-MHC complexes are displayed. However, the functional avidity of influenza-specific Trms has not been previously compared with that of other memory CD8 T cell subsets. In this article, a methodology is presented to compare the functional avidity of CD8 T cell subsets across murine tissues, with a focus on influenza-specific mLNs compared with splenic CD8 T cells, by stimulating both populations in the same well to account for CD8 T cell-extrinsic variables. The functional avidity of influenza-specific mLN effector CD8 T cells is slightly increased relative to splenic effector CD8 T cells. However, CD103⁺ mLN Trms display increased functional avidity compared with splenic memory CD8 T cells and CD103^- memory CD8 T cells within the mLN. In contrast, lung-derived CD103⁺ Trms did not exhibit enhanced functional avidity. mLN CD103⁺ Trms also exhibit increased TCR expression, providing a potential mechanism for their enhanced functional avidity.