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

Abstract

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-γ mRNA. The response in the draining lymph nodes, on the other hand, was dominated by CD4⁺ T cells (CD4/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-γ 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.