Synovial fluid MHC-unrestricted gamma delta-T lymphocytes contribute to antibacterial and anti-self cytotoxicity in the spondylarthropathies.

OBJECTIVE

In reactive arthritis (ReA), synovial fluid-derived bacteria-specific CD4+ and CD8+ T cells have been studied intensively in recent years. We have addressed the question whether gamma delta-TCR+ lymphocytes could contribute to antibacterial or anti-self cytotoxicity in the affected joints of patients, with spondylarthropathies.

METHODS

T cell clones were derived by random cloning from the synovial fluids of one patient with Yersinia-induced ReA, one patient with a Yersinia-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 expressing V gamma 9) were tested in a standard 52Cr-release assay using autologous or allogeneic B cell lines, CIR-B27, Daudi cells, and RJ.225 cells.

RESULTS

Four gamma delta-TCR+ clones killed both autologous and allogeneic target cells when infected with live Yersinia or Salmonella and also uninfected Daudi cells expressing GroEL heatshock protein. One clone was specific for Yersinia-infected targets. Three gamma delta-TCR+ clones were cytotoxic when uninfected autologous or allogeneic 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 contribute to antibacterial immunity via specific target cell lysis. Furthermore, anti-self cytolytic gamma delta-T cells could participate in the clearance of stressed and detrimental cells in the arthritic joint or, alternatively, could support the chronicity of autoimmune arthritis.