Sustained cross-presentation capacity of murine splenic dendritic cell subsets in vivo

Abstract

An exclusive feature of dendritic cells (DCs) is their ability to cross-present exogenous antigens in MHC class I molecules. We analyzed the fate of protein antigen in antigen presenting cell (APC) subsets after uptake of naturally formed antigen-antibody complexes in vivo. We observed that murine splenic DC subsets were able to present antigen in vivo for at least a week. After ex vivo isolation of four APC subsets, the presence of antigen in the storage compartments was visualized by confocal microscopy. Although all APC subsets stored antigen for many days, their ability and kinetics in antigen presentation was remarkably different. CD8α⁺ DCs showed sustained MHC class I-peptide specific CD8⁺ T-cell activation for more than 4 days. CD8α^- DCs also presented antigenic peptides in MHC class I but presentation decreased after 48 h. In contrast, only the CD8α^- DCs were able to present antigen in MHC class II to specific CD4⁺ T cells. Plasmacytoid DCs and macrophages were unable to activate any of the two T-cell types despite detectable antigen uptake. These results indicate that naturally occurring DC subsets have functional antigen storage capacity for prolonged T-cell activation and have distinct roles in antigen presentation to specific T cells in vivo.

Keywords: Antigen presentation/processing; CD4 T cells; CD8 T cells; Cross presentation/priming; Dendritic cells.