Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences.
Bacterial genomic DNA, plasmid DNA (pDNA) and synthetic oligodeoxynucleotides (ODN) containing immunostimulatory DNA sequences (ISS) have been proposed to foster a Th1 response via the release of type 1 cytokines from macrophages, dendritic cells, NK cells and B cells. In this study, we show that ISS-enriched DNA up-regulates a distinct profile of cell surface molecules on macrophages and B cells in vitro and in vivo. ISS-ODN and ISS-containing pDNA enhanced the expression of antigen presentation molecules (MHC class I and II), co-stimulatory molecules (B7-1, B7-2 and CD40), cytokine receptors (IFN-gamma receptor and IL-2 receptor), an adhesion molecule (ICAM-1) and an Fc receptor (Fcgamma receptor) on murine B cells or bone marrow-derived macrophages. The increased expression of these surface molecules is seen in purified cell populations and is largely independent of the effects of type 1 cytokines. Splenic antigen-presenting cells stimulated with ISS-ODN in vivo efficiently activate naive T cells and bias their differentiation toward a Th1 phenotype in vitro. Thus, the induction of both type 1 cytokines and a distinct profile of cell surface molecules contributes to the potent immunostimulatory effects of ISS-containing DNA on innate and adaptive immunity.
Martin-Orozco
E
E
Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Kobayashi
H
H
Van Uden
J
J
Nguyen
M D
MD
Kornbluth
R S
RS
Raz
E
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D004269:DNA, Bacterial / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009841:Oligonucleotides / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D004279:DNA, Viral; D008565:Membrane Proteins; D009841:Oligonucleotides