The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo.
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.
Iyoda
Tomonori
T
Department of Animal Development and Physiology, Graduate School of Biostudies. Department of Zoology, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Shimoyama
Susumu
S
Liu
Kang
K
Omatsu
Yoshiki
Y
Akiyama
Yuji
Y
Maeda
Yasuhiro
Y
Takahara
Kazuhiko
K
Steinman
Ralph M
RM
Inaba
Kayo
K
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism*; D016923:Cell Death; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D009997:Osmotic Pressure; D010587:Phagocytosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens