Rheumatoid Arthritis: A Disease of T-Lymphocyte/Macrophage Immunoregulation

Electron microscopic study of HLA‐DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane

“…A close spatial relationship between T cells and non-T DR+ cells has been observed in RA synovium by immunofluorescent and immunoperoxidase staining at the light microscopic level (13)(14)(15)(16)(17)(18)(19)(20)36,37). Klareskog et a1 (13) noted perivascular clusters of T cells of the helperhnducer type that were in close contact with DR+ cells in lymphoid aggregates.…”

“…The DR+ cells, on the basis of their light microscopic appearance, were described as having a "macrophage/dendritic" structure. Other investigators (18)(19)(20) have suggested that these DR+ cells were IDC, of the type seen in T cell areas of lymph nodes, which might function as antigen-presenting cells in the synovium. However, these cells have not been previously examined in the EM, and their structural characteristics have remained uncertain, particularly since they have been identified mainly by immunofluorescent staining (1 [8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…In particular, we examined the distribution of cells staining positively with anti-HLA-DR and antimonocyte/macrophage monoclonal antibodies in different regions of the synovial membrane. By use of light microscopic staining techniques, DR+ cells have been previously described in all regions of the synovium (13)(14)(15)(16)(17)(18)(19)(20)(35)(36)(37). However, the cells so stained have not been identified on the basis of their morphologic appearance.…”

Intraarticular variation in synovitis. Local macroscopic and microscopic signs of inflammatory activity are significantly correlated

“…Due to the variegated picture that emerged when the microscopic patterns were characterized in the various parts of the single joint, it was not considered feasible to assign anatomic designations to tentatively defined structures recently suggested to participate in specific immune reactions (12,16,20,24,25). Rather was it quite difficult, especially in synovitis with high microscopic activity, to discern the limits of the various perivascular and focal aggregates of infiltrating cells (Figure 1).…”

“…According to this concept, a singular histopathologic pattern, most often observed in randomly obtained tissue, has been assumed to represent not only the entire joint, but also particular diagnoses (4- 8,12,15,16,21,22), disease states (8)(9)(10)14,32,40), and specific pathogenetic mechanisms (12,14,16,(18)(19)(20)(23)(24)(25)40); the macroscopic and microscopic intraarticular variability of synovitis first reported 50 years ago is thereby disregarded (27,29).…”