RESPONSIVENESS OF HUMAN T-LYMPHOCYTES TO BACTERIAL SUPERANTIGENS PRESENTED BY CULTURED RHEUMATOID-ARTHRITIS SYNOVIOCYTES

Objective. Type B fibroblastic synoviocytes are abundant in inflamed j oints of patients with rheumatoid arthritis (RA), and can secrete cyto kines and other mediators of inflammation, The aim of this study was t o determine whether cell lines derived from RA type B synoviocytes cou ld also serve as accessory cells for T Lymphocyte activation. Methods. Cells from RA synoviocyte lines, with or without preculture in interf eron-gamma (IFN gamma), were cultured with purified peripheral blood T cells, in the presence or absence of superantigens or other accessory cell-dependent T cell mitogens, T cell proliferation was measured by thymidine incorporation, and synoviocyte surface markers were analyzed by flow cytometry. Results. RA type B synoviocyte lines were potent a ccessory cells for T cell responses to bacterial superantigens or lect ins, and direct cell-cell contact was required, Preculture in IFN gamm a augmented synoviocyte expression of major histocompatibility complex (MHC) class II molecules and of ligands for some T cell costimulatory receptors, but synoviocyte accessory cell function was evident even i n the absence of IFN gamma, Blocking studies using monoclonal antibodi es supported the notion of a role for CD2, CD11a/CD18 and MHC class II molecules in synoviocyte-dependent T cell activation. Monoclonal anti bodies against IFN gamma, interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha failed to block the T cell proliferati ve responses, but anti-IL-2 was strongly inhibitory. Conclusion. Cultu red RA type B synoviocytes can perform some of the functions of profes sional antigen-presenting cells, If such cells have similar properties in vivo, they may be important participants in activation of immune r esponses, in addition to their previously described synthetic and proi nflammatory roles, If RA synovial tissue T cells, like normal peripher al blood T cells, can respond to superantigens presented by synoviocyt es, this interaction could be important in the pathogenesis of RA.