title: Role of Toll-like receptors in costimulating cytotoxic T cell responses.
abstract: Stimulation of Toll-like receptors (TLR) by pathogen-derived compounds leads to activation of APC, facilitating the induction of protective immunity. This phenomenon is the basis of most adjuvant formulations currently in development. Here, we tested the ability of TLR2, 3, 4, 5, 7 and 9 signaling to enhance CTL responses upon vaccination with virus-like particles. Stimulation of TLR2 and 4 failed to increase CTL responses, whereas ligands for TLR3, 5 and 7 exhibited moderate adjuvant function. In contrast, stimulation of TLR9 dramatically increased CTL responses, indicating that ligands for TLR9 are likely to be the most promising candidates for the development of novel adjuvant formulations for stimulating CTL responses.
authors.affiliation: Cytos Biotechnology AG, Zürich, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Tazio
authors.initials: T
authors.lastname: Storni
authors.forename: Vania
authors.initials: V
authors.lastname: Manolova
authors.forename: Arnaud
authors.initials: A
authors.lastname: Didierlaurent
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Sirard
authors.forename: Peter
authors.initials: P
authors.lastname: Röthlisberger
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D018899:CpG Islands / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D005408:Flagellin / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006801:Humans; D000077271:Imiquimod; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014611:Vaccination; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D015703:Antigens, CD; D000956:Antigens, Viral; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C408982:CPG-oligonucleotide; C497965:Cd86 protein, mouse; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D006512:Hepatitis B Core Antigens; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495368:TLR6 protein, human; C495371:TLR9 protein, human; C495369:Tlr6 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D005408:Flagellin; D000077271:Imiquimod