HLA-DR4Dw4-restricted T cell recognition of self antigen(s) in the rheumatoid synovial compartment

Deirdre Devereux, Robyn E. O'hehir, James Mcguire, Wim C.A. Van Schooten, Jonathan R. Lamb, L. Steinman

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21 Citations (Scopus)

Abstract

The pathogenesis of joint destruction in rheumatoid arthritis remains III 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 thepresence of IL-2. After 2 weeks, the non-adherent cells were phenotyped as CD3-positive and TCR αβ-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 monomorphlc 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 resultsof these experiments suggest the presence of an MHC class ll-restricted antigen in the rheumatoid arthritis synovial compartment that induces proliferation of in vivo activated T cells.

Original languageEnglish
Pages (from-to)635-640
Number of pages6
JournalInternational Immunology
Volume3
Issue number7
DOIs
Publication statusPublished - 1 Jul 1991
Externally publishedYes

Keywords

  • Autoimmunity
  • Rheumatoid arthritis
  • T cells

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