Cell-cell interactions in synovitis. Interactions between T lymphocytes and synovial cells

Abstract

Mechanisms whereby T lymphocytes contribute to synovial inflammation in rheumatoid arthritis are poorly understood. Here we review data that indicate an important role for cell contact between synovial T cells, adjacent macrophages and fibroblast-like synoviocytes (FLS). Thus, T cells activated by cytokines, endothelial transmigration, extracellular matrix or by auto-antigens can promote cytokine, particularly TNF alpha, metalloproteinase production by macrophages and FLS through cell-membrane interactions, mediated at least through beta-integrins and membrane cytokines. Since soluble factors thus induced may in turn contribute directly to T cell activation, positive feedback loops are likely to be created. These novel pathways represent exciting potential therapeutic targets.

Figure 1

Pathways by which T cell interactions can contribute to synovial inflammation. T cells activated by cytokine combinations, by contact between extracellular matrix and endothelium and potentially by autoantigen, can activate the production of cytokines, MMPs and prostaglandins (PGs) by macrophages and FLS, creating potential positive feedback loops, and leading in turn to articular damage. Contact interactions might be variably mediated through adhesion molecules or membrane cytokines. The parallel secretion of pro-inflammatory and anti-inflammatory cytokines and cytokine receptors further modulate responses. The production by FLS of cytokines, such as IL-7, IL-15 and IL-18, that activate T cells is likely, but because few studies have yet directly addressed this issue, these pathways have been omitted. Interactions between synovial T and B lymphocytes are beyond the scope of this review.