Cross-presentation of cell-associated antigens by CD8α+ 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 naive 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.