title: Toll-like receptor ligand links innate and adaptive immune responses by the production of heat-shock proteins.
abstract: The report shows that CpG can exert additional adjuvant effects by inducing cells that are normally inferior antigen (Ag)-presenting cells to participate in immune induction by cross-priming. Macrophages (Mphi) exposed to protein Ag in the presence of bioactive CpG DNA released material that induced primary CD8(+) T cell responses in DC-naïve T cell cultures. This cross-priming event was accompanied by up-regulation of the stress protein response as well as inflammatory cytokine expression in treated Mphi. The material released was indicated to contain inducible heat shock protein-70 and epitope peptide, which in turn, were presented by dendritic cells (DCs) to responder T cells. Such an adjuvant effect by CpG may serve to salvage immunogenic material from otherwise inert depot cellular sites and additionally stimulate DCs to effectively cross-prime. The cross-priming, shown also to occur in vivo, may be particularly useful when Ag doses are low and have minimal opportunity for delivery to DCs for consequent direct priming.
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville 37996, USA.
authors.forename: Udayasankar
authors.initials: U
authors.lastname: Kumaraguru
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pack
authors.forename: Barry T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D011796:Quinacrine / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology; D051193:Toll-Like Receptors; D014162:Transfection; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D004527:Egg Proteins; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C110366:OVA-8; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D010047:Ovalbumin; D011796:Quinacrine