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

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.

• Authors: 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
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 71 Issue 10 Pg. 1706-15 (Oct 2012) ISSN: 1468-2060 [Electronic] England
• PMID: 22562976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Chaperonin 60
• Epitopes, T-Lymphocyte
• Oligodeoxyribonucleotides
• Toll-Like Receptor 9
• Vaccines, Subunit

Topics

• Adjuvants, Immunologic (administration & dosage)
• Administration, Intranasal
• Animals
• Arthritis, Experimental (immunology)
• Arthritis, Rheumatoid (immunology)
• Chaperonin 60 (administration & dosage, immunology)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Epitopes, T-Lymphocyte (immunology)
• Lymphocyte Activation (immunology)
• Male
• Oligodeoxyribonucleotides (administration & dosage, immunology)
• Rats
• Rats, Inbred Lew
• T-Lymphocytes, Regulatory (immunology)
• Toll-Like Receptor 9 (agonists)
• Vaccines, Subunit (administration & dosage, immunology)