Macrophage subpopulations in rheumatoid synovium: Reduced CD163 expression in CD4+ T lymphocyte–rich microenvironments

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Abstract
Objective The cell surface glycoprotein CD163 is a member of the cysteine‐rich scavenger receptor family, highly specific for leukocytes of the mononuclear phagocyte lineage. In vitro, it is induced by glucocorticoids, interleukin‐6 (IL‐6), and IL‐10 and down‐regulated by interferon‐γ (IFNγ), indicating that it has a role in antiinflammatory or other immunomodulatory pathways. We assessed CD163 expression in microenvironments within rheumatoid arthritis (RA) synovium to clarify the relationships among CD4+ T lymphocytes, IFNγ, and macrophage function in RA. Methods Double immunofluorescence and serial immunoenzymatic studies were performed on normal, osteoarthritic, and RA synovium and tonsil with antibodies to CD163, CD45, CD68, CD14, CD3, CD4, CD8, CD19, and IFNγ. Results CD163 was observed on all CD14+ cells in synovium and tonsil with the exception of cells within larger T lymphocyte clusters in synovium and within tonsillar follicles. All brightly CD14+ cells in or around vessel walls (interpreted as immigrant monocytes) were CD163+. CD163 labeled fewer cells than did CD68 in synovial intima, but all CD45+ intimal cells were CD163+. CD4+,IFNγ+ T lymphocytes in RA synovium were chiefly localized within clusters containing CD68+, CD163− cells. Conclusion Within RA synovium, CD163 has major advantages as a macrophage marker and does not appear to be restricted to “mature” macrophages. CD163 discriminates between synovial macrophages and synovial intimal fibroblasts, which also stain positively for CD68 in diseased tissue.