Submitted July 5, 2006
Accepted November 13, 2006
Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T cell and IgG2a response
Carole Bourquin*, Laura Schmidt, Veit Hornung, Cornelia Wurzenberger, David Anz, Nadja Sandholzer, Susanne Schreiber, Andreas Voelkl, Gunther Hartmann, and Stefan Endres
Division of Clinical Pharmacology, Dept of Internal Medicine, Ludwig-Maximilian University of Munich, Munich, Germany
Division of Clinical Pharmacology, University Hospital, University of Bonn, Bonn, Germany
* Corresponding author; email: carole.bourquin{at}med.uni-muenchen.de.
Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA, isRNA) are potent inducers of interferon-
via the Toll-like receptor 7. We investigated the effect of isRNA on the development of an immune response. We show that isRNA activates dendritic cells and induces production of Th1-type cytokines both in vitro and in vivo. Cytokine production led to bystander activation of T and B cells. We further demonstrate that isRNA triggers the generation of antigen-specific cytotoxic T cells and of an IgG2a-biased antibody response to antigen in a sequence-dependent manner. In summary, we provide evidence for the first time that isRNA oligonucleotides can simultaneously activate the innate and adaptive arms of the immune system.
