The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo

TLDR

Dendritic cells can phagocytose and present antigens from infected, malignant, and allogeneic cells in culture. The study used CFSE‑labeled apoptotic splenocytes, tumor cells, and NK‑killed allogeneic B cells, showing that only CD8+ DCs endocytose them, form MHC II–peptide complexes, and selectively present cell‑associated antigens to CD4+ and CD8+ T cells. In vivo and in vitro, only CD8+ DCs actively endocytose dying cells and present their antigens, whereas both DC subsets phagocytose latex particles and present soluble ovalbumin, confirming that CD8+ DCs are specialized for capturing dying cells and cross‑presenting cellular antigens.

Abstract

Dendritic cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic cells. Here we show directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected cells include syngeneic splenocytes and tumor cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B cells killed by NK cells in situ. The CFSE-labeled cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II–peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present cell-associated antigens to both CD4+ and CD8+ T cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying cells. In contrast, both CD8+ and CD8− DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying cells, and this helps to explain their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells.