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Cross-presentation of cell-associated antigens (Ag) plays an important role in the induction of anti-tumor responses, autoimmune diseases, and transplant rejection. While several dendritic cell (DC) populations can induce pro-inflammatory CD8(+) T cell responses to cell-associated Ag during infection, in the absence of infection, cross-priming of naïve CD8(+) T cells is highly restricted. Comparison of the main splenic DC populations in mice - including the classic, cross-presenting CD8α DC and the recently described merocytic DC (mcDC) - reveals that cross-priming DCs display a distinct phenotype in cell-associated Ag uptake, endosomal/lysosomal trafficking, lysosomal acidification, and Ag persistence compared to non-cross-priming DC populations. Although the CD8α DC and mcDC subsets utilize similar processing pathways to cross-present cell-associated Ag, cross-priming by CD8α DCs is associated with IL-12 production, while the superior priming of the mcDC is critically dependent on type I IFN production. This discussion illustrates how subtle differences in internal processing pathways and their signaling sequelae significantly affect the duration of Ag cross-presentation and cytokine production by DCs, thereby shaping the ensuing CD8(+) T cell response.

Cross-Presentation of Cell-Associated Antigens by Mouse Splenic Dendritic Cell Populations