SYNOVIAL-FLUID MHC-UNRESTRICTED GAMMA-DELTA-T LYMPHOCYTES CONTRIBUTE TO ANTIBACTERIAL AND ANTI-SELF CYTOTOXICICTY IN THE SPONDYLARTHROPATHIES

Objective. In reactive arthritis(ReA), synovial fluid-derived bacteria -specific CD4(+) and CD8(+) T cells have been studied intensively in r ecent years. We here addressed the question whether gamma delta-TCR(+) lymphocytes could contribute to antibacterial or anti-self cytotoxici cty in the affected joints of patients with spondylarthropathies. Meth ods. T cell clones were derived by random cloning from the synovial fl uids of one patient with Yersinia-induced ReA, one patient with a Yers inia-induced flare up of pre-existing ankylosing spondylitis, and one patient with ankylosing spondylitis. Eight clones with a CD3(+), alpha beta-TCR(-), CD4(-), CD8(-) and gamma delta-TCR(+) phenotype (all exp ressing V gamma 9) were tested in a standard Cr-52-release assay using autologous or allogeneic B cell lines, CIR-B27, Daudi cells, and RJ.2 25 cells. Results. Four gamma delta-TCR(+) clones killed both autologo us and allogeneic target cells when infected with live Yersinia or Sal monella and also uninfected Daudi cells expressing GroEL heatshock pro tein. One clone was specific for Yersinia-infected targets. Three gamm a delta-TCR(+) clones were cytotoxic when uninfected autologous or all ogeneic targets were employed Polymorphic ''classical'' MHC class I or class II molecules were not used as restriction elements.Conclusion. We conclude that, upon in vivo contact with bacteria such as Yersinia and Salmonella, synovial gamma delta-T lymphocytes are activated and c ontribute to antibacterial immunity via specific target cell lysis. Fu rthermore, anti-self cytolytic gamma delta-T cells could participate i n the clearance of stressed and detrimental cells in the arthritic joi nt or alternatively, could support the chronicity of autoimmune arthri tis.