CD40L (CD154) expression in human liver allografts during chronic ductopenic rejection

The CD40-CD40L (CD154) interaction plays a pivotal role in the effector mec hanisms of allograft rejection. Blockade of the CD40/CD40L costimulatory pa thway prevents the development of chronic allograft rejection in several an imal transplant models. The relevance of in situ CD40 and CD40L expression in human liver allografts was assessed by immunohistochemistry during ducto penic chronic rejection (CR), In CR allograft specimens (n = 8), marked CD4 0L expression was detected on Kupffer cells (KCs) and sinusoidal macrophage s with a unique centrilobular distribution (P <.001). The CD40L+ KCs and ma crophages were shown to be CD68+ after immunohistochemical analysis of seri al sections with anti-CD68 monoclonal antibody. Moderate staining of vascul ar and sinusoidal endothelial cells and mononuclear infiltrates was observe d in some CR cases. These findings were in contrast to the absence of CD40L expression in controls (n = 11) consisting of stable liver allograft and n ormal liver tissue specimens. Only occasional CD40 expression in some cases of CR and controls was observed. In CR, CD40L (CD154) expression is manife sted on KCs and macrophages. The present novel data show another important cellular source of CD40L expression and suggest a potential role of KCs/mac rophages and CD40/CD40L costimulatory interactions in the pathogenesis of c hronic rejection ductopenic liver allograft. Copyright (C) 1999 by the Amer ican Association for the Study of Liver Diseases.