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. |
Keywords: |
controlled study; nonhuman; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; immune system; dendritic cell; animal experiment; animal model; in vivo study; mice, inbred balb c; mice, inbred c57bl; mice, transgenic; models, animal; liver; dendritic cells; immune response; recombinant fusion proteins; nucleotide sequence; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; listeriosis; listeria monocytogenes; diphtheria toxin; sensitization; receptors, cell surface; malaria; t lymphocyte antigen; glycoprotein p 15095; priority journal; article; plasmodium yoelii; integrin alphaxbeta2
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