Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins.
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.
Sparwasser
T
T
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Vabulas
R M
RM
Villmow
B
B
Lipford
G B
GB
Wagner
H
H
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D004269:DNA, Bacterial / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D019013:CD40 Antigens; D023201:CD40 Ligand; D004269:DNA, Bacterial; D015226:Dinucleoside Phosphates; D010047:Ovalbumin; C015772:CpG dinucleotide