Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins

Eur J Immunol. 2000 Dec;30(12):3591-7. doi: 10.1002/1521-4141(200012)30:12<3591::AID-IMMU3591>3.0.CO;2-J.

Abstract

Receptors for conserved molecular patterns associated with microbial pathogens induce synthesis of co-stimulatory molecules and cytokines in immature dendritic cells (DC), as do antigen-reactive CD4 T helper cells via CD40 signaling. Once activated, antigen-presenting DC may activate CD8 T cell responses in a T helper cell-independent fashion. Using immunostimulatory CpG-oligonucleotides (ODN) mimicking bacterial CpG-DNA, we tested whether CpG-DNA bypasses the need for T helper cells in CTL responses towards proteins by directly activating antigen-presenting DC to transit into professional APC. We describe that immature DC in situ constitutively process soluble proteins and generate CD8 T cell determinants yet CD8 T cell responses remain abortive. Induction of primary antigen-specific CD8 cytotoxic T lymphocyte (CTL)-mediated responses becomes initiated in wild-type as well as T helper cell-deficient mice, provided soluble protein and CpG-ODN are draining into the same lymph node. Specifically we show that CpG-ODN trigger antigen-presenting immature DC within the draining lymph node to acutely up-regulate co-stimulatory molecules and produce IL-12. These results provide new insights for generating in vivo efficient CTL responses to soluble proteins which may influence vaccination strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Antigens / physiology
  • CD40 Ligand / physiology
  • DNA, Bacterial / pharmacology*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Dinucleoside Phosphates / pharmacology*
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / physiology*

Substances

  • CD40 Antigens
  • DNA, Bacterial
  • Dinucleoside Phosphates
  • CD40 Ligand
  • cytidylyl-3'-5'-guanosine
  • Ovalbumin