In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens.
Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York 10016, USA. s.jung@weizmann.ac.il
Steffen
S
Jung
Derya
D
Unutmaz
Phillip
P
Wong
Gen-Ichiro
G
Sano
Kenia
K
De los Santos
Tim
T
Sparwasser
Shengji
S
Wu
Sri
S
Vuthoori
Kyung
K
Ko
Fidel
F
Zavala
Eric G
EG
Pamer
Dan R
DR
Littman
Richard A
RA
Lang
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004167:Diphtheria Toxin / Q000276:immunology; D066257:Heparin-binding EGF-like Growth Factor; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D008089:Listeria monocytogenes / Q000276:immunology; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D010967:Plasmodium yoelii / Q000276:immunology / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D016167:Integrin alphaXbeta2; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins