Role of endothelium in chronic inflammatory synovitis

The rheumatoid synovial membrane is infiltrated by chronic inflammatory cells. The major fraction of the infiltrating lymphocytes is composed of CD4+ cells. A large number of studies of the composition of the T cell receptors of these lymphocytes have failed to demonstrate evidence of a dominant clonal population of T cells which is characteristic of rheumatoid synovitis. Most of the T cells are polyclonal in nature. This report discusses the basis for this polyclonality. Current evidence is reviewed which supports the conclusion that T cells emigrate from postcapillary venules because they are in an activated state. The activated T cell is characterized by elevated expression and avidity of adhesion receptors capable of reacting with counterreceptors on the endothelial cells of postcapillary venules, leading to binding and emigration from the blood. The T cells are retained in the perivascular connective tissue because their adhesion receptors interact with counterreceptors on other mononuclear cells and on matrix proteins. The increased expression of adhesion receptors on the T cells may be a result of prior contact with antigen; increased expression of counter-receptors on the endothelial cells results from stimulation by cytokines released by local inflammatory cells. The interaction between T cell adhesion molecules and counterreceptors is independent of the immunological specificity of the T cell. Hence, the T cells of the rheumatoid synovium are largely polyclonal memory cells.