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  • Title: HLA-DR4Dw4-restricted T cell recognition of self antigen(s) in the rheumatoid synovial compartment.
    Author: Devereux D, O'Hehir RE, McGuire J, van Schooten WC, Lamb JR.
    Journal: Int Immunol; 1991 Jul; 3(7):635-40. PubMed ID: 1911537.
    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.
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