Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs

Influenza infections induce a rapid, but transient, dendritic cell (DC) migration from the lungs to the lymph nodes (LNs) that is followed by substantial recruitment of DCs into the lungs without subsequent migration to the LNs. Given that peripheral DCs are primarily thought to be involved in the initiation of adaptive immunity after migration into lymphoid tissues, what role these newly lung-recruited DCs play in influenza virus immunity is unclear. In this study, we demonstrate that loss of non-LN migratory pulmonary DC subsets increases mortality, sustains higher viral titers, and impairs pulmonary CD8 T cell responses. Reconstitution of the lungs with pulmonary plasmacytoid DCs, CD8 alpha(+) DCs, or interstitial DCs restores CD8 T cell responses in a cell contact -, major histocompatability complex I-, and influenza peptide-dependent manner. Thus, after their initial activation in the LN, protective influenza-specific CD8 T cell responses require additional antigen-dependent interactions, specifically with DCs in the lungs.