Identification of immunostimulatory dendritic cells in the synovial effusions of patients with rheumatoid arthritis.

Abstract

Dendritic cells in the circulation are leukocytes that are rich in Ia antigens and that actively stimulate T cell replication. We have identified dendritic cells in the joint effusions of patients with rheumatoid arthritis. By phase-contrast and immunofluorescence microscopy, synovial mononuclear cells contained 1-5% dendritic profiles that were rich in HLA-DR and DQ, had small amounts of C3bi receptor, and lacked a battery of monocyte and lymphocyte markers. These dendritic cells could be enriched to 604-0% purity by cytolytic depletion of monocytes and lymphocytes with a group of monoclonal antibodies (MAb) and complement. By transmission electron microscopy, the dendritic cell processes were bulbous in shape and lacked organelles. The cytoplasm had few lysosomes or endocytic vacuoles but contained a well-developed smooth reticulum that was comparable to that previously described in the ia-rich interdigitating cells of lymphoid tissues.

Dendritic cells and the pathogenesis of rheumatoid arthritis

“…DC have been identified in rheumatoid ST and SF by several groups over the last 15 years, and elucidation of their derivation, function, and potential role in the pathogenesis of the disease is increasingly better understood [1,2,[9][10][11][12][13][14][15][16][17][18][19][20]. Myeloid DC can be identified and freshly purified from normal or RA peripheral blood (PB), RA SF, or ST cell suspensions through the use of a combination of myeloid markers, and it is therefore possible to directly compare the phenotype and function of PB and SF DC.…”

“…SF DC and PB DC stimulated resting allogeneic T cells with equivalent efficacy, and more efficiently than SF monocytes. However, SF DC were markedly more efficient simulators of autologous T cells in the absence of exogenous antigen (autologous MLR) [11,16,17,21]. Many investigators have been able to demonstrate the presence of autoreactive T cells in RA, both by the autologous MLR and by deriving clones from PB, SF, or ST, and it appears likely that autoreactive T cells are expanded in the circulation of these patients and their unaffected first degree relatives [22][23][24][25].…”

Differences in responses of normal and rheumatoid arthritis peripheral blood t cells to synovial fluid and peripheral blood dendritic cells in allogeneic mixed leukocyte reactions

“…The purity of dendritic cell-enriched cell populations thus obtained varied from 50% to 80%, as estimated on the basis of characteristic dendritic cell morphology and strong HLA-DQ expression. For some experiments, further dendritic cell enrichment was accomplished by treating the cells with anti-CD3 (Becton Dickinson, Mountain View, CA) and 63D3 (Bethesda Research Laboratories, Gaithersburg, MD) monoclonal antibodies and rabbit complement (Cedarlane, Hornby, Ontario, Canada) as previously described (21).…”

Role of Bone Marrow in the Pathogenesis of Rheumatoid Arthritis

“…Unlike intimal macrophages, the precise origin of type B synoviocytes remains unclear, although they are thought to arise from the sublining tissue or other support structures of a joint (Firestein,1996). On the other hand, a number of studies have shown that peripheral blood dendritic cells (DC) accumulate in the synovium, where they undergo phenotypic and functional differentiation in situ (Zvaifler et al,1985;Thomas et al,1994). It has been also shown that synovial DC gradually lose their dinstinct morphologic appearance and become indistinguishable from fibroblasts in vitro (Hendler et al,1985).…”