Stimulation of suppressive T cell responses by human but not bacterial 60-kD heat-shock protein in synovial fluid of patients with rheumatoid arthritis.

Abstract

In several animal models of rheumatoid arthritis (RA), T cell responses to self 60-kD heat-shock protein 60 (hsp60) protect against the induction of arthritis. The nature of this suppressive T cell activity induced by self hsp60 is not clear.

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

“…Earlier studies in patients with JIA and patients with RA, using whole Hsp60 proteins, suggested that T cell recognition of human Hsp60 is associated with a regulatory phenotype (26,29,31). Interestingly, in our study, the human Hsp60 epitopes also induced a more antiinflammatory T cell response, as depicted by marked changes in the IL-10:TNF␣ ratio.…”

“…Although immune recognition of whole mycobacterial and whole human Hsp60 in PBMCs and synovial fluid mononuclear cells from patients with RA is well documented (26,36,(45)(46)(47)(48), no Hsp60 T cell epitope that is recognized in a majority of RA patients has yet been identified. By using a computer algorithm that can predict the potential pan-DR-binding motifs (34), we identified 8 potential T cell epitopes derived from both microbial and human Hsp60.…”

“…First, experiments in the adjuvantinduced arthritis model suggest that Hsp60 might play a crucial role in the immune regulation of arthritis (25). Second, in RA, as well as in juvenile idiopathic arthritis (JIA), Hsp60 of microbial origins as well as those of endogenous origins are targets of immune responses (26,27). In the spontaneous remitting form of JIA (oligoarticular JIA), T cells reactive to self Hsp60 at the onset of disease are associated with disease remission (28) and have a striking regulatory phenotype (29).…”

“…In the spontaneous remitting form of JIA (oligoarticular JIA), T cells reactive to self Hsp60 at the onset of disease are associated with disease remission (28) and have a striking regulatory phenotype (29). In RA, T cells stimulated with human Hsp60 display a marked suppressive phenotype, compared with T cells stimulated with homologous mycobacterial Hsp65 (26). Thus, Hsp60 self-reactive T cells may play a role in modulating chronic arthritis (adjuvant-induced arthritis, RA, and JIA), underscoring their potential as candidate antigens to modulate the immune response in chronic arthritis (24,30).…”

Heat-shock proteins induce T-cell regulation of chronic inflammation

“…7 45 Moreover, among patients with rheumatoid arthritis, those with HSP60-reactive synovial T cells acquired the regulatory phenotype on in vitro restimulation with self-HSP60 and suppressed production of tumour necrosis factor by autologous blood T cells. 46 Initial clinical trials using HSPs and HSP-derived peptides showed promising results in dampening the clinical disease score in ongoing disease. 8 11 12 In conclusion, it is clear that HSP proteins and peptides have an immunomodulatory role.…”