Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis

Graeff-Meeder, E. R. De; Rijkers, Ger T.; Kuis, Wietse; Zegers, B. J. M.; Zee, Ruurd van der; Schuurman, H. J.; Bijlsma, J. W. J.; Eden, Willem van

doi:10.1016/0140-6736(91)93057-g

Cited by 190 publications

(96 citation statements)

References 25 publications

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“…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).…”

mentioning

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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mentioning

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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“…In vitro study of the immunological basis of many human autoimmune diseases has been hampered by failure to identify, and to isolate and purify, the relevant autoantigens in their natural form. Several different approaches have been used to compensate for the non-availability of natural human autoantigen in the study of autoreactive B and T cell responses, including the use of sequence-specific peptides [1][2][3], of recombinant proteins over-expressed in bacteria [4][5][6], and of equivalent proteins purified from tissue obtained from other species [7,8]. None of these approaches is wholly satisfactory, each having theoretical and practical disadvantages.…”

Section: Introductionmentioning

confidence: 99%

T cell responses to natural human proteins in primary biliary cirrhosis

Jones¹,

Palmer²,

Yeaman³

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe study of T cell responses to autoantigens in human autoimmunity has been hampered by difficulties, firstly in identifying significant autoantigens, and secondly in the purification of authentic human proteins in sufficient quantities to allow characterization of antigen-specific T cell responses. In this study we have purified a human autoantigen, pyruvate dehydrogenase, retaining its enzymatic activity, and characterized autoreactive T cell responses to it in a human autoimmune disease, primary biliary cirrhosis. T cell responses to a mixture of the E2 and protein X subunits of human pyruvate dehydrogenase complex are seen in most affected patients, but in only a small minority of normal and chronic liver disease controls. By contrast, responses to whole pyruvate dehydrogenase complex occur with equal frequency in both groups. This suggests that responses to the E2 component/protein X of pyruvate dehydrogenase complex play a role in the pathogenesis of primary biliary cirrhosis. The availability of significant quantities of the human autoantigen in primary biliary cirrhosis makes this condition an interesting model in which to study true autoreactive human T cell responses.

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“…Proliferative responses to human Hsp60 were frequently observed in patients with remitting pauciarticular JIA and not in patients with progressive polyarticular or systemic JIA (79)(80)(81). In longitudinal studies, spontaneous remission was found to be preceded by elevated responses, which declined after remission.…”

Section: Discussionmentioning

confidence: 85%

Immune regulation in adjuvant‐induced arthritis: Possible implications for innovative therapeutic strategies in arthritis

Eden¹,

Waksman²

2003

Arthritis & Rheumatism

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Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis

Cited by 190 publications

References 25 publications

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

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

T cell responses to natural human proteins in primary biliary cirrhosis

Immune regulation in adjuvant‐induced arthritis: Possible implications for innovative therapeutic strategies in arthritis

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