Basis for defective responses of rheumatoid arthritis synovial fluid lymphocytes to anti-CD3 (T3) antibodies.
Synovial fluid mononuclear cells (SFMC) from patients with active rheumatoid arthritis characteristically respond poorly to mitogens. In this study, mitogenic antibodies reactive with the CD3(T3) antigen on human T lymphocytes were used to analyze the basis for the deficiency. OKT3-induced proliferation and release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from SFMC were depressed in all patients. Purified IL-1 or recombinant IL-2 restored proliferative responses in SFMC and increased IL-2 receptor density. Exogenous IL-1 also enhanced IL-2 release. Fractionation of SFMC supernatants on phosphocellulose columns revealed the presence of IL-1 and a potent IL-1 inhibitor. The monocyte-derived IL-1 inhibitor blocked IL-1-dependent responses of normal peripheral blood lymphocytes to OKT3, but had no effect on IL-2-dependent events. These results suggest that IL-1 inhibitor(s) in SFMC impair(s) OKT3-induced mitogenesis by interfering with the effects of IL-1 on T lymphocytes. The net result is deficient IL-2 secretion, IL-2 receptor expression, and impaired cellular proliferation. This novel inhibitory circuit provides a rational explanation for the diminished function of synovial fluid T lymphocytes in rheumatoid arthritis patients.
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007375:Interleukin-1; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007213:Indomethacin