Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8(+) T cell responses to influenza

The question of which dendritic cells (DCs) respond to pulmonary antigens and cross-prime CD8(+) T cells remains controversial. We show that influenza-specific CD8(+) T cell priming is controlled by different DCs at different times after infection. Whereas early priming is controlled by both CD103(+)CD11b(lo) and CD103(-)CD11b(hi) DCs, CD103(-)CD11b(hi) DCs dominate antigen presentation at the peak of infection. Moreover, CD103(-)CD11b(hi) DCs capture exogenous antigens in the lung and directly cross-prime CD8(+) T cells in the draining lymph node without transferring antigen to CD8α(+) DCs. Finally, we show that CD103(-)CD11b(hi) DCs are the only DCs to express CD70 after influenza infection and that CD70 expression on CD103(-)CD11b(hi) DCs licenses them to expand CD8(+) T cells responding to both influenza and exogenous ovalbumin.