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.
Jung
Steffen
S
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York 10016, USA. s.jung@weizmann.ac.il
Unutmaz
Derya
D
Wong
Phillip
P
Sano
Gen-Ichiro
G
De los Santos
Kenia
K
Sparwasser
Tim
T
Wu
Shengji
S
Vuthoori
Sri
S
Ko
Kyung
K
Zavala
Fidel
F
Pamer
Eric G
EG
Littman
Dan R
DR
Lang
Richard A
RA
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