In Vivo Depletion of CD11c+ Dendritic Cells Abrogates Priming of CD8+ T Cells by Exogenous Cell-Associated Antigens

Immunity. 2002 Aug;17(2):211-20. doi: 10.1016/s1074-7613(02)00365-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Diphtheria Toxin / immunology
  • Heparin-binding EGF-like Growth Factor
  • Integrin alphaXbeta2 / genetics
  • Integrin alphaXbeta2 / immunology*
  • Intercellular Signaling Peptides and Proteins
  • Listeria monocytogenes / immunology
  • Liver / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Animal
  • Plasmodium yoelii / immunology
  • Plasmodium yoelii / physiology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Diphtheria Toxin
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Integrin alphaXbeta2
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins