Anti-viral CD8+ T cell Effector Activity Is Regulated by Hematopoietic Cells in the Influenza-Infected Lung Parenchyma (130.16)

Abstract

Abstract CD8+ T cell effector activity is instrumental in the resolution of influenza infection, as well as additional respiratory viral infections, by their ability to eliminate infected cells and to release potent cytokines. CD8+ T cells localized to the lung airways are believed to be responsible for this anti-viral activity because CD8+ T cells located in the lung parenchyma have limited access to the respiratory epithelium, the principal site of influenza replication. To test this hypothesis, we utilized the detection of CD8+ T cell IFN? production ex vivo and in vivo as a convenient means to identify influenza-specific CD8+ T cells and to define the location of antigen presentation within the influenza-infected lungs. Surprisingly, influenza-specific CD8+ T cells collected from the airways produced limited amounts of IFN? in vivo. In contrast, significant numbers of influenza-specific CD8+ T cells in the lung parenchyma were actively producing IFN?. Because IFN? production by CD8+ T cells is principally TCR dependent, data indicated antigen engagement occurs in the lung parenchyma, not the airways. Because the lung parenchyma is enriched in hematopoietic (CD45+) cells compared to the airways, it was hypothesized that these cells were the primary antigen presenting cells in the lungs. To test this hypothesis, H-2Kb-/-Db-/- mice were irradiated and reconstituted with H-2Kb+/+Db+/+ bone marrow. Despite the absence of MHC class I on respiratory epithelial cells, CD8+ T cells in the lung parenchyma produced significant amounts of IFN? in vivo. These observations challenge conventional knowledge on the mechanism by which CD8+ T cells clear virally-infected cells in the respiratory epithelium.