title: Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: E
authors.initials: E
authors.lastname: Martin-Orozco
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: J
authors.initials: J
authors.lastname: Van Uden
authors.forename: M D
authors.initials: MD
authors.lastname: Nguyen
authors.forename: R S
authors.initials: RS
authors.lastname: Kornbluth
authors.forename: E
authors.initials: E
authors.lastname: Raz
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D004279:DNA, Viral; D008565:Membrane Proteins; D009841:Oligonucleotides