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Pathways of mononuclear cell infiltration in rheumatoid synovitis

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Summary

The mononuclear cell infiltration which characterizes the chronic inflammatory reaction results from the migration of lymphocytes and monocytes through the endothelium of the postcapillary venule. The initial step in the emigration of these cells in their binding to the vascular endothelium. The binding capacity of the endothelial cell (EC) for lymphocytes and monocytes is increased by IFN-γ, IL-1, TNFα, and TNFβ. Production of these cytokines by chronic inflammatory cells may be expected to amplify the chronic inflammatory reaction. Initiation of the chronic synovitis of rheumatoid and other chronic synovitides probably results from the interaction of antigen with sensitized T cells in the sublining region of the synovium. This interaction is facilitated by the presence of substantial numbers of DR+macrophage+accessory cells in the synovial interstitial space. It is likely that these accessory cells are bone marrow derived monocytes migrating to the synovial lining layer in response to chemotactic factors released by the hyperplastic synovial lining cells. Lymphocytes differ in their binding affinity for ECs, and more strongly binding lymphocytes may be preferentially bound. Since binding is the first step in lymphocyte emigration, this event may lead to the selection of more strongly binding lymphocytes in the perivascular infiltrate. The T cells present in the mononuclear cell infiltrates of rheumatoid arthritis, other chronic synovitides, and multiple sclerosis have been shown to be composed largely of the CDw29+CD4+, helper-inducer, memory cell subset. The predominance of this T-cell subset may result from its demonstrated greater binding affinity for ECs. The fact that this subset has been shown to react weakly with T-cell mitogens and strongly with soluble antigens, may explain two important properties of synovial fluid T cells in inflammatory disease: (1) their weak reactivity to T cells mitogens and (2) their strong reactivity to antigens. Thus, the hyperplasia of the synovial lining layer, which may be an important factor in the mobilization of accessory cells, and the increased EC binding of HI memory T cells may combine to facilitate the initiation and maintenance of chronic synovitis.

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  1. Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA

    M. Ziff

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Ziff, M. Pathways of mononuclear cell infiltration in rheumatoid synovitis. Rheumatol Int 9, 97–103 (1989). https://doi.org/10.1007/BF00271865

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