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 language | English |
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Pages (from-to) | 1706-1715 |
Number of pages | 10 |
Journal | Annals of the Rheumatic Diseases |
Volume | 71 |
Issue number | 10 |
DOIs | |
Publication status | Published - 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