Rheumatoid non-lymphoid synovial cells and the induction of mixed leukocyte reactions. Low-density preparations containing Ia+ macrophages and dendritic cells are less stimulatory than peripheral blood non-T cells.

Interactions of autologous or allogeneic T cells with non-lymphoid synovial cells were investigated to study the mechanisms of T-cell activation in rheumatoid arthritis. The synovial cell fraction obtained by Percoll gradients contained an average of 31% cells positive for monocyte antigens and 62% intensely Ia-positive cells. Tissue cultures demonstrated large numbers of cells with a dendritic morphology. Mixed leukocyte reaction (MLR) cultures between these synovial cell preparations and autologous or allogeneic peripheral blood T cells as responder cells revealed low T-cell responsiveness with an average of 3900 dpm or 17 800 dpm, respectively, in contrast to 16 900 dpm or 79 600 dpm, using rheumatoid peripheral blood non-T cells (P less than 0.01), despite equivalent amounts of Ia antigens on both stimulator populations, as determined by cell-sorter analysis. The addition of indomethacin to these synovial cell/T cell co-cultures resulted in an enhancement of T-cell responsiveness; however, this increase did not reach statistical significance due to large test variations. Co-cultures of non-lymphoid synovial cells and PHA-stimulated autologous T cells induced a marked inhibition of T-cell proliferation that could partially be reversed by the addition of indomethacin. The reduction of monocyte-antigen-positive cells by depletion of iron phagocytic cells did not result in a significant enhancement of T-cell responsiveness. These data demonstrate that the majority of non-lymphoid synovial cells, despite the presence of large amounts of Ia-antigens, are not potent inducers of T-cell proliferation and strong suppressing cells in polyclonal T-cell activation. These effects do not appear to reside in the macrophage fraction alone and can only partly be attributed to the action of prostaglandins.