Characterization of an immediate splenic precursor of CD8+ dendritic cells capable of inducing antiviral T cell responses

J Immunol. 2009 Apr 1;182(7):4200-7. doi: 10.4049/jimmunol.0802286.

Abstract

Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8(+)CD24(+) DC (CD8(+) DC), and conventional CD8(-)CD24(-) DC (CD8(-) DC). We have previously shown that CD8(+) DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8(+) DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8(-)CD24(+) DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8(-)CD24(+) DC represent an immediate precursor of CD8(+) DC, as demonstrated by their expression pattern of characteristic markers of CD8(+) DC, their capacity to cross-present in vitro, and their conversion into CD8(+) DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8(-)CD24(+) DC in vivo was greatly enhanced as compared with terminally differentiated CD8(+) DC. Moreover, in a vaccination protocol, CD8(-)CD24(+) DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8(+) DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8(+) DC that does not yet express CD8. The enhanced capacity of CD8(-)CD24(+) DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation / immunology
  • Blotting, Western
  • CD24 Antigen / immunology
  • CD24 Antigen / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Cell Differentiation
  • Cross-Priming / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Herpesvirus 1, Human / immunology*
  • Histocompatibility Antigens Class I
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Spleen / cytology
  • Spleen / immunology
  • Stem Cells / cytology
  • Stem Cells / immunology*
  • Stem Cells / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology

Substances

  • CD24 Antigen
  • CD8 Antigens
  • Histocompatibility Antigens Class I