Immunity
Volume 17, Issue 2, August 2002, Pages 211-220
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Article
In Vivo Depletion of CD11c+ Dendritic Cells Abrogates Priming of CD8+ T Cells by Exogenous Cell-Associated Antigens

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Abstract

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.

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Correspondence: Richard A. Lang; e-mail: [email protected], and Dan R. Littman; e-mail: [email protected]

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Present address: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.

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Present address: Vanderbilt University Medical School, Department of Microbiology and Immunology, Nashville, Tennessee 37232.

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Present address: Divisions of Developmental Biology and Ophthalmology, Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229.