TLR9 agonist CpG enhances protective nasal HSP60 peptide vaccine efficacy in experimental autoimmune arthritis

Evelien Zonneveld-Huijssoon, Femke van Wijk, Sarah Roord, Eveline Delemarre, Jenny Meerding, Wilco de Jager, Mark Klein, Eyal Raz, Salvatore Albani, Wietse Kuis, Marianne Boes, Berent J. Prakken*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1706-1715
Number of pages10
JournalAnnals of the Rheumatic Diseases
Volume71
Issue number10
DOIs
Publication statusPublished - 2012

Keywords

  • REGULATORY T-CELLS
  • HEAT-SHOCK-PROTEIN
  • JUVENILE IDIOPATHIC ARTHRITIS
  • COLLAGEN-INDUCED ARTHRITIS
  • DENDRITIC CELLS
  • INTERFERON-GAMMA
  • IMMUNE-RESPONSES
  • ORAL TOLERANCE
  • IN-VIVO
  • INDOLEAMINE 2,3-DIOXYGENASE

Fingerprint

Dive into the research topics of 'TLR9 agonist CpG enhances protective nasal HSP60 peptide vaccine efficacy in experimental autoimmune arthritis'. Together they form a unique fingerprint.

Cite this