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Integrin signalling defects in T-lymphocytes in systemic lupus erythematosus

I E Collins

Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London

S B Kanner

Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington, USA

M J Humphries

Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester, UK

N Amft

Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London;Present address; Department of Rheumatology, University of Birmingham Medical School, UK

R G Wickremasinghe

Department of Haematology, Royal Free Hospital, London, UK

D D'Cruz

Department of Rheumatology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London

K E Nye

Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London;Department of Immunology, 38 Little Britain, London EC1A 7BE, UK.

W JW Morrow

Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London

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.

Key Words: fibronectin • integrin • protein kinase C • signalling • SLE • T cell co-stimulation

Lupus, Vol. 8, No. 1, 39-51 (1999)
DOI: 10.1191/096120399678847371


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