Cross-presentation of cell-associated antigens by CD8alpha+ dendritic cells is attributable to their ability to internalize dead cells.

In the mouse, cross-presentation is an exclusive property of the CD8alpha+ subset of dendritic cells (DC) but the basis for this selectivity remains unclear. Here we report that splenic CD8alpha+ DC are much superior to other DC subsets in internalizing dying cells in vitro. In contrast, CD8alpha+, CD8alpha- CD4+ and CD8alpha- CD4- DC subsets phagocytose bacteria or latex beads to a similar extent. Although CD8alpha+ DC are better than CD4+ DC at presenting ovalbumin (OVA)-loaded splenocytes to naïve OT-I T lymphocytes, CD4+ DC are better at presenting OVA-expressing Escherichia coli to the same T cells. In both cases, presentation is abrogated by lactacystin. These results show that both splenic CD8alpha+ and CD8alpha- DC can present exogenous antigens on major histocompatibility complex (MHC) class I via a proteasome-dependent pathway and suggest that the specialized cross-presenting function of CD8alpha+ DC is a result of their ability to endocytose dying cells rather than a unique pathway for handling endosomal contents.