ABNORMAL T-CELL COSTIMULATION BY PROTEINS OF THE EXTRACELLULAR-MATRIX IN HUMAN RENAL ALLOGRAFTING

T cells interact with extracellular matrix (ECM) proteins as they pass through the endothelium and move about in various microenvironments. Recent data indicate that such proteins provide strong costimulation to CD3-TCR-complex-mediated T-cell activation. Thus, ECM proteins can regulate T-cell responses via their integrin and non-integrin receptors. We have shown that the costimulating activity of interstitial ECM proteins (collagen type I, fibronectin) is abolished in renal allograft recipients treated with cyclosporin A (CsA) but not azathioprine. In contrast, cyclosporin treatment does not affect potent costimulation provided by the major component of basement membranes, collagen type IV. We suggest that these disturbances in T-cell interactions with ECM proteins caused by CsA therapy may contribute to cyclosporin-induced transplant arteriosclerosis.