Functionally distinct T cells in three compartments of the respiratory tract after influenza virus infection

This study aimed to resolve, firstly, whether T cell responses induced in one tissue site are similar to those induced by the same antigen in another site and, secondly, whether influenza virus infection induces one predominant type of T cell response locally in the respiratory tract. To address these questions, T cell responses in three compartments of the respiratory tract were compared after infection of mice with a sublethal dose of influenza virus: the draining mediastinal lymph nodes (MLN), the lung parenchyma and the airways. Each compartment harbored a T cell response substantially different from that found at the other sites. A preferential accumulation of ex vivo-cytolytic CD8+ T cells was found in the airways (CD4/CD8 ratio 1:2) and to a lesser extent in the lung parenchyma (CD4/CD8 ratio 1:1). T cells from both compartments expressed high levels of various cytokine mRNA, but showed differences in their respective expression pattern, with those from lung tissue showing particularly high levels of IFN-gamma mRNA. The response in the draining lymph nodes, on the other hand, was dominated by CD4(+) T cells (CD3/CD8 ratio 2:1) with a higher proliferative capacity (after TCR/CD3 cross-linking) and which provided better B cell help in vitro than CD4(+) T cells isolated from lung tissue. T cells from MLN expressed mRNA for a variety of cytokines with only low levels of IFN-gamma mRNA and they showed no CTL activity ex vivo. These functional differences were not due to differences in the kinetics of the response, or to the higher frequencies of activated T cells in lung tissue and airways compared to MLN, since the differences remained when cell-sorter-purified activated (CD18(hi), CD44(hi)) T cells from MLN and lung tissue were compared in a time-course study. Taken together, these findings indicate that pathogens such as influenza virus induce a heterogenous set of T cell responses in different tissue sites affected by the infection.