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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2953-2960.
Prepublished online as a Blood First Edition Paper on November 28, 2006; DOI 10.1182/blood-2006-07-033258.
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IMMUNOBIOLOGY
Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response
Carole Bourquin1,
Laura Schmidt1,
Veit Hornung1,
Cornelia Wurzenberger1,
David Anz1,
Nadja Sandholzer1,
Susanne Schreiber1,
Andreas Voelkl1,
Gunther Hartmann2, and
Stefan Endres1
1 Division of Clinical Pharmacology, Department of Internal Medicine, Ludwig-Maximilian University of Munich, Germany;
2 Division of Clinical Pharmacology, University Hospital, University of Bonn, Germany
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.
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