PT - JOURNAL ARTICLE AU - Evelien Zonneveld-Huijssoon AU - Femke van Wijk AU - Sarah Roord AU - Eveline Delemarre AU - Jenny Meerding AU - Wilco de Jager AU - Mark Klein AU - Eyal Raz AU - Salvatore Albani AU - Wietse Kuis AU - Marianne Boes AU - Berent J Prakken TI - TLR9 agonist CpG enhances protective nasal HSP60 peptide vaccine efficacy in experimental autoimmune arthritis AID - 10.1136/annrheumdis-2011-201131 DP - 2012 Oct 01 TA - Annals of the Rheumatic Diseases PG - 1706--1715 VI - 71 IP - 10 4099 - http://ard.bmj.com/content/71/10/1706.short 4100 - http://ard.bmj.com/content/71/10/1706.full SO - Ann Rheum Dis2012 Oct 01; 71 AB - Objectives 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.