title: HLA-DR4Dw4-restricted T cell recognition of self antigen(s) in the rheumatoid synovial compartment.
abstract: The pathogenesis of joint destruction in rheumatoid arthritis remains ill defined, although it is thought to be the result of tissue damage mediated by T cells. This prompted us to isolate and characterize in vivo activated T cells from rheumatoid arthritis synovial fluid in an attempt to determine their specificity. Heterogeneous synovial fluid cells, containing both adherent and non-adherent cell types, were recovered from joint aspirates and cultured in the presence of IL-2. After 2 weeks, the non-adherent cells were phenotyped as CD3-positive and TCR alpha beta-positive T cells. Polyclonal T cell lines were derived from four rheumatoid arthritis patients; of these, two proliferated, in a dose-dependent manner to only autologous synovial fluid in the presence of autologous or DR4Dw4 histocompatible antigen presenting cells. T cell proliferation to the synovial fluid could be inhibited by monomorphic anti-HLA-DR monoclonal antibody, but not by anti-DQ or anti-class I antibodies. T cell clones were established by limiting dilution of a synovial T cell line in the presence of autologous synovial fluid and DR4Dw4 histocompatible accessory cells. Examination of the antigen specificity of these T cell clones demonstrated that they were reactive with a component of synovial fluid. The results of these experiments suggest the presence of an MHC class II-restricted antigen in the rheumatoid arthritis synovial compartment that induces proliferation of in vivo activated T cells.
authors.affiliation: ImmuLogic Pharmaceutical Corporation, Palo Alto, CA 94304.
authors.forename: D
authors.initials: D
authors.lastname: Devereux
authors.forename: R E
authors.initials: RE
authors.lastname: O'Hehir
authors.forename: J
authors.initials: J
authors.lastname: McGuire
authors.forename: W C
authors.initials: WC
authors.lastname: van Schooten
authors.forename: J R
authors.initials: JR
authors.lastname: Lamb
mesh_terms: D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D001324:Autoantigens; D002999:Clone Cells / Q000276:immunology; D015804:HLA-DR4 Antigen; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D015804:HLA-DR4 Antigen; D007376:Interleukin-2