T cells in reactive arthritis.

T cells appear to play a major role in the development, maintenance and also resolution of reactive arthritis (ReA). Recent advances in understanding the processes involved in T cell activation now allow us to examine the peripheral blood and synovial fluid T cell responses to given "arthritogenic" microorganisms in terms of antigen specificity, epitope identification, cytokine secretion patterns, HLA restriction and the role of different T cell subsets in ReA. Peripheral blood bulk proliferation and limiting dilution studies provide evidence that the peripheral T cell response against arthritis-associated gram-negative bacteria is decreased in patients developing immunological sequelae such as ReA after gastrointestinal infection. Using clonal analysis of synovial fluid CD4+ T cells it has been shown that a polyclonal rather than an oligoclonal response to a variety of bacterial antigens is induced at the site of synovitis and that these CD4+ T cells produce a Th1-type of cytokine. 65 kD heat shock protein may represent one of the possible linkages of anti-infectious and autoimmune reactions. Furthermore, a spectrum of killer cells is present in the synovial fluid of patients with ReA. This spectrum of cytotoxic T cells includes antigen-specific, class I-restricted alpha beta-TCR+CD8+ lymphocytes, antigen-specific, apparently non-MHC-restricted alpha beta-TCR+CD8+ lymphocytes and gamma delta-TCR+ cells with braod cytolytic activity directed against bacteria-infected target cells. HLA-B27-restricted Yersinia- or Salmonella-specific synovial fluid CD8+ T cells may provide the missing link between genetic disposition (HLA-B27) and extra-articular infection with arthritogenic bacteria in these patients.