title: TLR9 agonist CpG enhances protective nasal HSP60 peptide vaccine efficacy in experimental autoimmune arthritis.
abstract: OBJECTIVE
  Peptide-based immune tolerance induction is considered an attractive treatment option for autoimmune diseases. The authors have developed a novel method that can enhance the induction of protective peptide-specific T-cell responses, using a rat arthritis model. The authors focused on the Toll-like receptor 9 ligand CpG, which was shown to stimulate regulatory T-cell proliferation when added to plasmacytoid dendritic cells (pDC) using in-vitro cultures.
  
  
  METHODS
  The peptide used is a heat shock protein 60 epitope (p1) that elicits tolerogenic peptide-specific immune responses in human arthritis patients and was recently shown to have protective capacity as a bystander antigen in the rat adjuvant arthritis model. Rats were treated with three nasal doses of p1, CpG or a combination of p1 and CpG. Antigen-presenting cells were studied in nose-draining lymph nodes (mandibular lymph nodes; MLN) after nasal treatment, and T-cell responses were analysed in joint-draining lymph nodes after arthritis induction.
  
  
  RESULTS
  Nasal co-administration of p1/CpG significantly augmented the arthritis-protective effect of p1, while CpG treatment alone did not. Co-treatment of p1/CpG increased both the number and activation status of pDC in draining MLN, which was accompanied by amplified p1-specific T-cell proliferation and interleukin (IL)-10 production. During early arthritis, p1-specific IL-10 production was identified at the site of inflammation. P1 and p1/CpG-treated rats showed a greater amount of CD4+FoxP3+ regulatory T cells in the joint-draining lymph nodes, which correlated with lower arthritis scores.
  
  
  CONCLUSIONS
  These clinical and immunological data suggest the use of CpG as a potent adjuvant for mucosal peptide-specific immune therapy in arthritis.
authors.affiliation: Department of Pediatric Immunology, University Medical Centre Utrecht, Centre for Molecular and Cellular Intervention, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
authors.forename: Evelien
authors.initials: E
authors.lastname: Zonneveld-Huijssoon
authors.forename: Femke
authors.initials: F
authors.lastname: van Wijk
authors.forename: Sarah
authors.initials: S
authors.lastname: Roord
authors.forename: Eveline
authors.initials: E
authors.lastname: Delemarre
authors.forename: Jenny
authors.initials: J
authors.lastname: Meerding
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Mark
authors.initials: M
authors.lastname: Klein
authors.forename: Eyal
authors.initials: E
authors.lastname: Raz
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
authors.forename: Wietse
authors.initials: W
authors.lastname: Kuis
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D018834:Chaperonin 60; D018984:Epitopes, T-Lymphocyte; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D022223:Vaccines, Subunit