Dendritic cells and high endothelial venules in the rheumatoid synovial membrane

Since dendritic cells are believed to play a crucial role in the pathogenesis of rheumatoid arthritis (RA) we studied the microenvironmental relationship of these cells with endothelial cells, lymphocytes and macrophages in the rheumatoid synovial membrane. With the monoclonal antibodies OKIa (MHC Class II determinants), RFD1 and L25 (both specific for "active" human dendritic cells) we identified large numbers of dendritic cells. With the monoclonal antibody HECA 452 specific for a putative adhesion molecule notably present on high endothelial venules (HEV)], a subset of dendritic cells could be detected. HECA-452 positive dendritic cells were found in 2 basic patterns: (1) associated with small lymphoid cell clusters in the neighborhood of vessels with flat, HECA-452 negative endothelium, (2) at the periphery of dense organoid lymphoid infiltrates, surrounding HECA-452 positive HEV-like vessels. Our data suggest that the influx of HECA-452, L25, RFD1 and MHC Class II positive dendritic cells is an early event in the development of the inflammatory infiltrate found in the rheumatoid synovial membrane. The formation of organoid lymphoplasmacellular infiltrates with high endothelial venules would be secondary to this event.