Open AccessResponsiveness of human T lymphocytes to bacterial superantigens presented by cultured rheumatoid arthritis synoviocytes
Author(s) -
Tsai Carlene,
Diaz Luis A.,
Singer Nora G.,
Li Lan Lan,
Kirsch Anita H.,
Mitra Raj,
Nickoloff Brian J.,
Crofford Leslie J.,
Fox David A.
Publication year - 1996
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780390117
Subject(s) - superantigen , t cell , immunology , cytokine , antigen presenting cell , major histocompatibility complex , tumor necrosis factor alpha , biology , microbiology and biotechnology , antigen , medicine , immune system
Objective . Type B fibroblastic synoviocytes are abundant in inflamed joints of patients with rheumatoid arthritis (RA), and can secrete cytokines and other mediators of inflammation. The aim of this study was to determine whether cell lines derived from RA type B synoviocytes could also serve as accessory cells for T lymphocyte activation. Methods . Cells from RA synoviocyte lines, with or without preculture in interferon‐γ (IFNγ), 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 accessory cells for T cell responses to bacterial superantigens or lectins, and direct cell‐cell contact was required. Preculture in IFNγ 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 in the absence of IFNγ. Blocking studies using monoclonal antibodies supported the notion of a role for CD2, CD11a/CD18 and MHC class II molecules in synoviocyte‐dependent T cell activation. Monoclonal antibodies against IFNγ, interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor α failed to block the T cell proliferative responses, but anti–IL‐2 was strongly inhibitory. Conclusion . Cultured RA type B synoviocytes can perform some of the functions of professional antigen‐presenting cells. If such cells have similar properties in vivo, they may be important participants in activation of immune responses, in addition to their previously described synthetic and proinflammatory roles. If RA synovial tissue T cells, like normal peripheral blood T cells, can respond to superantigens presented by synoviocytes, this interaction could be important in the pathogenesis of RA.