Autoreactivity to human heat‐shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis

Prakken, A. B. J.; Eden, Willem van; Rijkers, Ger T.; Kuis, Wietse; Toebes, Elly A.H.; Graeff-Meeder, E. R. De; Zee, Ruurd van der; Zegers, B. J. M.

doi:10.1002/art.1780391108

Cited by 122 publications

(59 citation statements)

References 26 publications

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“…Recently, we found that a similar protective mechanism occurs upon immunization with Mt hsp70 (7). Moreover, T cell responses to human hsp60 have been associated with self-remitting forms of juvenile chronic arthritis (8).…”

mentioning

confidence: 85%

Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-γ and Are Protective in Adjuvant Arthritis

Paul

Kooten

Eden

et al. 2000

The Journal of Immunology

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Previously we have shown that T cell responses to the mycobacterial 60-kDa heat shock protein (hsp60) peptide M256–270 mediated protection against adjuvant arthritis in Lewis rats. We have demonstrated now that M256–270-primed T cells become highly reactive to naive syngeneic APC upon repetitive restimulation in vitro with peptide M256–265, comprising the conserved core of peptide M256–270. These autoproliferative responses in the absence of added Ag were MHC class II restricted and resulted in the production of IL-4/IL-10 and IFN-γ. Enhanced autoproliferation and expression of the cell surface molecule B7.2 by these T cells were observed in response to syngeneic heat-shocked APC, which indicated that the autoproliferation and expression of B7.2 resulted from the recognition of endogenously expressed and processed hsp. Despite their strong autoreactivity, upon transfer such T cells were found to induce a significant disease reduction in adjuvant arthritis. In contrast, T cells both primed and restimulated with peptide M256–270 became unresponsive toward syngeneic APC as well as toward the conserved core peptide M256–265, and they were devoid of protective capacity. This study demonstrates that the loss of self-tolerance toward hsp60 does not necessarily lead to autoimmune disease, but that hsp60-specific self-reactive and autoproliferative T cells may mediate T cell regulation in arthritis.

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confidence: 85%

Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-γ and Are Protective in Adjuvant Arthritis

Paul

Kooten

Eden

et al. 2000

The Journal of Immunology

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“…HSP immunisations have been shown to inhibit autoimmune disorders such as diabetes and arthritis both in animal models and in initial clinical trials in patients with chronic inflammatory disease. [5][6][7][8][9][10][11][12] Over the past years, several research groups have shown that HSP reactive T cells might play a role in this regulatory function and in the induction of anti-inflammatory cytokines in chronic inflammation.…”

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confidence: 99%

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

2005

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“…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 RA, T cells stimulated with human Hsp60 display a marked suppressive phenotype, compared with T cells stimulated with homologous mycobacterial Hsp65 (26).…”

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confidence: 99%

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

Jong¹,

Lafeber²,

Jager³

et al. 2009

Arthritis & Rheumatism

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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.

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Autoreactivity to human heat‐shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis

Cited by 122 publications

References 26 publications

Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-γ and Are Protective in Adjuvant Arthritis

Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-γ and Are Protective in Adjuvant Arthritis

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

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

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