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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2162-2169.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-04-1091.

Submitted April 8, 2003
Accepted October 17, 2003
CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro
Simon Rothenfusser, Veit Hornung, Maha Ayyoub, Stefanie Britsch, Andreas Towarowski, Anne Krug, Anja Sarris, Norbert Lubenow, Daniel Speiser, Stefan Endres, and Gunther Hartmann*
Division of Clinical Pharmacology, Department of Internal Medicine, University of Munich, Munich, Germany
Division of Clinical Onco-immunology, Centre Hospitalier Universitaire Vaudois (CHUV), Ludwig Institute for Cancer Research, Lausanne, Switzerland
Institute of Immunology and Transfusion Medicine, University of Greifswald, Greifswald, Germany
* Corresponding author; email: ghartmann{at}lrz.uni-muenchen.de.
Two distinct types of CpG ODN have been identified that differ in their capacity to stimulate antigen presenting cells: CpG-A induce high amounts of IFN- /- in plasmacytoid dendritic cells (PDC), while CpG-B induce PDC maturation and are potent activators of B cells, but stimulate only small amounts of IFN- /- . Here we examined the ability of these CpG ODN to enhance peptide specific CD8+ T cell responses in human PBMC. The frequency of influenza matrix specific "memory" CD8+ T cells was increased by both types of CpG ODN, while the frequency of Melan-A specific "naive" CD8+ T cells increased upon stimulation with CpG-B but not with CpG-A. The presence of PDC in PBMC was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- upon peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T cell clones both of which was IFN- /- dependent. In conclusion, CpG-B seems to be superior for priming of CD8+ T cell responses, while CpG-A selectively enhances memory CD8+ T cell responses and induce cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells.

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