Integrin signalling defects in T-lymphocytes in systemic lupus erythematosus

Objective: To establish the relationship between T cell responses to integr in coreceptor stimulation and B cell hyperreactivity as measured by patholo gic autoantibody production. Methods: Peripheral blood mononuclear cells from 42 patients with SLE accor ding to the American Rheumatism Association criteria were examined for thei r ability to adhere to plate-immobilised fibronectin. Go-stimulation assays were performed on the same cells using anti-CD3 antibody alone or co-immob ilised with an anti-beta(1)-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. beta(1)-Integrin expression was e stablished by FAGS analysis. Results: An impaired PKC response to integrin-mediated activation was found in T-lymphocytes from 6/21 (29%) SLE patients, which correlated significan tly with an absence of anti-dsDNA antibody in patient sera, irrespective of prednisolone treatment. Integrin co-stimulation of TcR/CD3-induced prolife ration 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 beta(1)-integrin signallin g pathways may influence pathological antibody production in SLE by affecti ng T-lymphocyte activation and interactions between T- and B-lymphocytes.