Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs

Nat Immunol. 2010 Apr;11(4):313-20. doi: 10.1038/ni.1848. Epub 2010 Feb 28.

Abstract

Cross-priming allows dendritic cells (DCs) to induce cytotoxic T cell (CTL) responses to extracellular antigens. DCs require cognate 'licensing' for cross-priming, classically by helper T cells. Here we demonstrate an alternative mechanism for cognate licensing by natural killer T (NKT) cells recognizing microbial or synthetic glycolipid antigens. Such licensing caused cross-priming CD8alpha(+) DCs to produce the chemokine CCL17, which attracted naive CTLs expressing the chemokine receptor CCR4. In contrast, DCs licensed by helper T cells recruited CTLs using CCR5 ligands. Thus, depending on the type of antigen they encounter, DCs can be licensed for cross-priming by NKT cells or helper T cells and use at least two independent chemokine pathways to attract naive CTLs. Because these chemokines acted synergistically, this can potentially be exploited to improve vaccinations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Cell Movement / immunology
  • Cell Separation
  • Chemokine CCL17 / immunology*
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*
  • Receptors, CCR4 / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Ccr4 protein, mouse
  • Chemokine CCL17
  • Receptors, CCR4