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

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Abstract
Efficient antiviral responses require cross-priming of cytolytic T lymphocytes by dendritic cells. Randall and colleagues show that CD103−CD11bhi dendritic cells directly cross-prime CD8+ T cells after influenza infection. The question of which dendritic cells (DCs) respond to pulmonary antigens and cross-prime CD8+ T cells remains controversial. We show here that influenza-specific CD8+ T cell priming was controlled by different DCs at different times after infection. Whereas early priming was controlled by both CD103+CD11blo and CD103−CD11bhi DCs, CD103−CD11bhi DCs dominated antigen presentation at the peak of infection. Moreover, CD103−CD11bhi DCs captured exogenous antigens in the lungs and directly cross-primed CD8+ T cells in the draining lymph nodes without transferring antigen to CD8α+ DCs. Finally, we show that CD103−CD11bhi DCs were the only DCs to express CD70 after influenza infection and that CD70 expression on CD103−CD11bhi DCs licensed them to expand CD8+ T cell populations responding to both influenza and exogenous ovalbumin.