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.
Department of Internal Medicine, Medical College, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China.
M F
MF
Liu
C Y
CY
Yang
J S
JS
Li
K A
KA
Lai
S C
SC
Chao
H Y
HY
Lei
D000069594:Abatacept; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018796:Immunoconjugates; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept