Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response.
Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA [isRNA]) are potent inducers of interferon-alpha 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.
Bourquin
Carole
C
Division of Clinical Pharmacology, Department of Internal Medicine, Ludwig-Maximilian University of Munich, Germany. carole.bourquin@med.uni-muenchen.de
Schmidt
Laura
L
Hornung
Veit
V
Wurzenberger
Cornelia
C
Anz
David
D
Sandholzer
Nadja
N
Schreiber
Susanne
S
Voelkl
Andreas
A
Hartmann
Gunther
G
Endres
Stefan
S
D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000494:pharmacology*; D000818:Animals; D000941:Antigens; D001483:Base Sequence; D002645:Chickens; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009843:Oligoribonucleotides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D009843:Oligoribonucleotides; D010047:Ovalbumin