Pan-DR-binding Hsp60 self epitopes induce an interleukin-10-mediated immune response in rheumatoid arthritis
| Autor: | Wietse Kuis, Huib de Jong, Berent J. Prakken, Margje H. Haverkamp, Johannes W. J. Bijlsma, Wilco de Jager, Salvatore Albani, Floris F. P. Lafeber |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Regulatory T cell medicine.medical_treatment T cell Immunology Molecular Sequence Data Epitopes T-Lymphocyte Lymphocyte proliferation Carboxyfluorescein diacetate succinimidyl ester Epitope Arthritis Rheumatoid chemistry.chemical_compound Immune system Rheumatology Immunology and Allergy Medicine Humans Pharmacology (medical) Amino Acid Sequence Renal disorder [IGMD 9] Aged Cell Proliferation Aged 80 and over HLA-D Antigens business.industry Chaperonin 60 Middle Aged Interleukin-10 Interleukin 10 Cytokine medicine.anatomical_structure chemistry Case-Control Studies Leukocytes Mononuclear Female business |
| Zdroj: | Arthritis and Rheumatism, 60, 1966-76 Arthritis and Rheumatism, 60, 7, pp. 1966-76 |
| ISSN: | 0004-3591 |
| Popis: | Item does not contain fulltext 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 alpha (TNFalpha), interleukin-1beta (IL-1beta), 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:TNFalpha ratio, compared with that of the microbial peptides. CONCLUSION: These results suggest a disease-specific 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. |
| Databáze: | OpenAIRE |
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