Analysis of CD154 and CD40 expression in native coronary atherosclerosis and transplant associated coronary artery disease

T cells have roles in the pathogenesis of native coronary atherosclerosis ( CA) and transplant-associated coronary artery disease (TCAD). The mechanism s by which T cells interact with other cells in these lesions are not fully known. CD154 is an activation-induced CD4(+) T cell surface molecule that interacts with CD40(+) target cells, including macrophages and endothelial cells, and induces the production of pro-inflammatory molecules, including CD54 (ICAM-1) and CD106 (VCAM-1). To investigate whether CD154-CD40 interac tions might be involved in the pathogenesis of CA or TCAD we performed immu nohistochemical studies of CD154 and CD40 expression on frozen sections of coronary arteries obtained from cardiac allograft recipients with CA (n=10) or TCAD (n=9). Utilizing four different anti-CD154 mAb we found that CD154 expression was restricted to infiltrating lymphocytes in CA and TCAD. CD40 expression was markedly up-regulated on intimal endothelial cells, foam ce lls, macrophages and smooth muscle cells in both diseases. Dual immunolabel ing demonstrated many CD40(+) cells co-expressed CD54 and CD106. The extent of CD40, CD54 and CD106 expression showed statistical significant correlat ion with the severity of disease and the amount of intimal lymphocytes. Tog ether these studies demonstrate the presence of activated CD154(+) and CD40 (+) cells in both CA and TCAD lesions and suggest that CD154-mediated inter actions with CD40(+) macrophages, foam cells, smooth muscle cells and/or en dothelial cells may contribute to the pathogenesis of these diseases.