Rheumatology Advance Access originally published online on June 29, 2005
Rheumatology 2005 44(10):1245-1254; doi:10.1093/rheumatology/keh724
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Expression and function of inducible costimulator on peripheral blood T cells in patients with systemic lupus erythematosus
Department of Laboratory Diagnosis and 1 Department of Rheumatology, Changhai Hospital, Second Military Medical University, Shanghai, P. R. China.
Correspondence to: Q. Shen, Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, 174# Changhai Road, Shanghai 200433, P. R. China. E-mail: yjhsmmu{at}yahoo.com.cn
Objective. To investigate the role of inducible costimulator (ICOS) in the pathogenesis of SLE, we assessed its expression on peripheral blood CD4 and CD8 T cells and functional roles in patients with systemic lupus erythematosus (SLE).
Methods. Expression of ICOS on peripheral blood CD4 and CD8 T cells and ICOS ligand (ICOSL) on peripheral blood CD19 B cells from patients with SLE, patients with rheumatoid arthritis (RA) and healthy volunteers were determined by two-colour flow cytometry. The functional costimulatory effects of ICOS on peripheral blood mononuclear cells (PBMC) were assessed by T-cell proliferative responses, cytokines, anti-double-stranded DNA (anti-dsDNA) antibody and total IgG production.
Results. Peripheral blood CD4 and CD8 T cells expressing ICOS were significantly increased in patients with SLE compared with patients with RA and healthy subjects. Peripheral blood CD19 B cells expressing ICOSL in SLE were markedly reduced compared with RA. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher than those of anti-CD3/hamster IgG (HIgG) in healthy subjects, but not in patients with SLE. Anti-CD3/ICOS-stimulated SLE PBMC secreted similar levels of IL-10 and IFN-
but a significantly lower level of IL-2 than healthy PBMC. Anti-CD3/ICOS-mediated costimulation significantly enhanced the production of anti-dsDNA antibodies and total IgG in patients with SLE.
Conclusion. Hyperexpression of ICOS on peripheral blood CD4 and CD8 T cells from patients with SLE contributed to the dysregulated T-cell proliferation, T-cell activation and pathogenic autoantibody production, which showed that the abnormality of ICOS costimulation may play an immunopathological role(s) in the pathogenesis of SLE.
KEY WORDS: Inducible costimulator, Systemic lupus erythematosus, Cytokines, Anti-dsDNA antibodies, Flow cytometry
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