Increased expression of down-regulatory CTLA-4 molecule on T lymphocytes from rheumatoid synovial compartment

Since the CTLA-4 molecule expressed on activated T lymphocytes has recently been suggested to be an important negative regulator in autoimmune diseases, this study was undertaken to investigate the expression and function of CTLA-4 on synovial T cells from patients with rheumatoid arthritis. CTLA-4-expressing T cells were detected using a dual fluorescence flow cytometric method. Only a small percentage of peripheral blood T cells from patients with rheumatoid arthritis had detectable surface CTLA-4 expression (mean +/- SD, 1. 89 +/- 1.92%). However, the levels of CTLA-4-positive T cells was increased significantly in rheumatoid synovial fluids (5.44 +/- 4. 96%) and synovial membranes (28.76 +/- 14.30%). To explore the role of CTLA-4 molecule in the inflammation of rheumatoid joints, CTLA-4 was blocked with anti-CTLA-4 antibody to assess its effects on the production of tumour necrosis factor alpha and interleukin 1beta in synovial fluid mononuclear cell culture. The addition of anti-CTLA-4 antibody enhanced the production of tumour necrosis factor alpha and interleukin 1beta in a dose-dependent manner. The data suggest that the expression of CTLA-4 plays a down-regulatory role in rheumatoid articular inflammation. We thus concluded that CTLA-4 was up-regulated on synovial T cells from patients with RA, and the increased CTLA-4 expression might exert a down-regulation effect on tumour necrosis factor alpha and interleukin 1beta production.