Synovial fluid transforming growth factor beta inhibits dendritic cell-T lymphocyte interactions in patients with chronic arthritis

Objective. To examine whether rheumatoid synovial fluid (SF) inhibits dendr itic cell (DC) expression of the CD80 and CD86 costimulator molecules and c ontributes to SF T lymphocyte hyporesponsiveness. Methods. Cell-free rheumatoid SF was tested for its effect on DC-stimulated autologous/allogeneic mixed lymphocyte reactions and for its effect on DC surface antigen expression, as assessed by flow cytometry. Blocking monoclo nal antibodies were used to identify the SF cytokines that inhibited DC-T l ymphocyte interactions. Results. Low concentrations of SF (2.5%) could inhibit DC-mediated autologo us and allogeneic T lymphocyte proliferation. This inhibitory effect could be reversed by neutralizing transforming growth factor beta (TGF beta) and interleukin-2 (IL-2), but not by IL-12, in the SF, Hyaluronic acid, IL-6, I L-10, and tumor necrosis factor alpha were not associated with SF inhibitio n. In vitro culture alone and crosslinking with the CD40 ligand up-regulate d DC CD80/CD86 expression and costimulator function, and this was not affec ted by inclusion of SF. In the presence of SF, DC clustered with autologous T lymphocytes showed decreased CD80 and CD86 expression, and variable CD80 /CD86 decreases were observed on DC clustered with allogeneic T lymphocytes . Conclusions. TGF beta in SF appears to suppress T lymphocyte function, whic h may affect both signaling to DC and the induction of DC costimulator func tion.