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.
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D010835:Phytohemagglutinins