FUNCTIONALLY DISTINCT T-CELLS IN 3 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 i n another site and, secondly, whether influenza virus infection induce s one predominant type of T cell response locally in the respiratory t ract. To address these questions, T cell responses in three compartmen ts of the respiratory tract were compared after infection of mice with a sublethal dose of influenza virus: the draining mediastinal lymph n odes (MLN), the lung parenchyma and the airways. Each compartment harb ored a T cell response substantially different from that found at the other sites. A preferential accumulation of ex vivo-cytolytic CD8+ T c ells was found in the airways (CD4/CD8 ratio 1:2) and to a lesser exte nt in the lung parenchyma (CD4/CD8 ratio 1:1). T cells from both compa rtments expressed high levels of various cytokine mRNA, but showed dif ferences in their respective expression pattern, with those from lung tissue showing particularly high levels of IFN-gamma mRNA. The respons e 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 d ifferences 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-sor ter-purified activated (CD18(hi), CD44(hi)) T cells from MLN and lung tissue were compared in a time-course study. Taken together, these fin dings indicate that pathogens such as influenza virus induce a heterog enous set of T cell responses in different tissue sites affected by th e infection.