PAN–DR‐Binding Hsp60 self epitopes induce an interleukin‐10–mediated immune response in rheumatoid arthritis

Abstract

Objective. Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60-directed responses in RA, it is necessary to study such responses at the molecular, epitope-specific level. This study was undertaken to characterize the disease specificity and function of pan-DR-binding Hsp60-derived epitopes as possible modulators of autoimmune inflammation in RA.Methods. Lymphocyte proliferation assays (using 3 H-thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls. Results. A disease (RA)-specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), and IL-10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4؉ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5-10-fold higher IL-10:TNF␣ ratio, compared with that of the microbial peptides.Conclusion. These results suggest a diseasespecific immune-modulatory role of epitope-specific T cells in the inflammatory processes of RA. Therefore, these pan-DR-binding epitopes could be used as a tool to study the autoreactive T cell response in RA and might be suitable candidates for use in immunotherapy.

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

“…Third, the increase in IL-10 could exceed the increase in IFNγ in p1/CpG combination treatment rats, possibly creating an anti-inflammatory environment. This cytokine pattern has earlier been observed in HSP epitope-specific T-cell responses of arthritis patients 1 71…”

Pep19 drives epitope spreading in periodontitis and periodontitis‐associated autoimmune diseases

“…Pep19 identified in our study is similar in its sequence to epitope peptide p1 reported by another group who have screened pan-DR-binding HSP60 self-epitopes using a computer algorithm (42). They reported induction of Tregs by peptide p1 for tolerogenic response in the management of juvenile idiopathic arthritis (41).…”

Bystander suppression of experimental arthritis by nasal administration of a heat shock protein peptide

“…p1 was originally selected based on a pan-DR binding motif and was found to induce a regulatory profile in PBMC of patients with chronic arthritis 15 42. To our knowledge, p1 is the first bystander epitope that is both recognised by the majority of RA and JIA patients and is effective in experimental arthritis.…”