Integrin signalling defects in T-lymphocytes in systemic lupus erythematosus
| Autor: | Martin J. Humphries, R. G. Wickremasinghe, S. B. Kanner, I. E. Collins, N. Amft, Tony Ng, K. E. Nye, W. J. W. Morrow, D. D'cruz |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Adolescent T-Lymphocytes T cell Integrin 030204 cardiovascular system & hematology Lymphocyte Activation Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine Rheumatology Cell Adhesion medicine Humans Lupus Erythematosus Systemic Phosphorylation Protein Kinase C B cell Protein kinase C Aged 030203 arthritis & rheumatology Lupus erythematosus biology business.industry Integrin beta1 Autoantibody Middle Aged medicine.disease Enzyme Activation Isoenzymes medicine.anatomical_structure Antibodies Antinuclear Immunology biology.protein Female Antibody business |
| Zdroj: | Lupus. 8:39-51 |
| ISSN: | 1477-0962 0961-2033 |
| DOI: | 10.1191/096120399678847371 |
| Popis: | Objective: To establish the relationship between T cell responses to integrin coreceptor stimulation and B cell hyperreactivity as measured by pathologic autoantibody production.Methods: Peripheral blood mononuclear cells from 42 patients with SLE according to the American Rheumatism Association criteria were examined for their ability to adhere to plateimmobilised fibronectin. Co-stimulation assays were performed on the same cells using anti-CD3 antibody alone or co-immobilised with an anti-b1-integrin antibody. Proliferative responses were measured by 3[H]thymidine pulsing on day 3 and activation was determined using a commercial protein kinase C assay, the protocol being established by our group in association with Promega. b1-Integrin expression was established by FACS analysis.Results: An impaired PKC response to integrin-mediated activation was found in T-lymphocytes from 6=21 (29%) SLE patients, which correlated significantly with an absence of anti-dsDNA antibody in patient sera, irrespective of prednisolone treatment. Integrin co-stimulation of TcR/CD3-induced proliferation and T cell adhesion to fibronectin were also impaired among 5=21 (24%) and 6=15 (40%) patients studied, respectively.Conclusion: We hypothesise that the integrity of b1-integrin signalling pathways may influence pathological antibody production in SLE by affecting T-lymphocyte activation and interactions between T and Blymphocytes. |
| Databáze: | OpenAIRE |
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