Prostanoid modulation of synovial antigen-specific CD4+ T-cell cytotoxic function in rheumatoid arthritis.
The recent demonstration of cytolytic mediators within synovial CD4+ T-cells of patients with rheumatoid arthritis (RA) has suggested an additional role for these cells in the pathogenesis of the disease. In this study we have investigated the function and regulation of antigen-specific class II-restricted cytotoxic T-cells from the synovial fluid (SFMNC) and peripheral blood (PBMNC) of 20 seropositive RA patients, and correlated in vitro findings with clinical data. Regulatory factors including prostaglandin E2 (PGE2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured in cell supernatants. A diversity in SFMNC antigen-specific cytotoxicity that correlated with therapy and PGE2 production was found, and shown to be mediated by synovial prostanoid (products of cyclooxygenase metabolism) inhibition of effector function. Our findings indicate that SFMNC cytotoxicity may be important in the pathogenesis and treatment of RA. Cyclooxygenase inhibition as the sole treatment early in RA may reduce the potentially beneficial inhibitory effect of synovial prostanoids on antigen-specific SFMNC cytotoxicity.
Ratcliffe
L T
LT
Department of Medicine, University of Cape Town, South Africa.
Lukey
P T
PT
Meyers
O L
OL
Ress
S R
SR
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002455:Cell Division; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000502:physiology*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D011453:Prostaglandins; D015232:Dinoprostone