Cellular and molecular parameters in human renal allograft rejection.
Acute rejection of human renal allografts is frequent postransplantation complication. In addition, it is a risk factor for chronic rejection, the most common cause of failure of long-term allografts. Renal allografts are rejected as a result of an immune response directed against alloantigens on the graft that are absent from the host, and the most important of these are the HLA antigens. The application of molecular diagnostic methods has revealed a differential intra-renal gene expression of cytokines, chemokines and their receptors, and cytotoxic attack molecules in acute and chronic rejection processes. Differential expression of T cell costimulatory molecules B7 and CD40/CD40L, and endothelium adhesion molecules ICAM-1 and VCAM-1 has also been reported during acute rejection. These molecules play an important role in mediating the recruitment of lymphocytes into rejecting allografts and costimulation of T cell activation. Based on experimental data, it seems that it is likely that the blockade of T cell costimulatory pathways can be used in human in the future to selectively prevent transplant rejection without generally suppressing the immune system.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104-4283, USA. malekkam@mail.med.upenn.edu
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D018122:B7-1 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D006084:Graft Rejection; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods*; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D018122:B7-1 Antigen; D019013:CD40 Antigens; D006680:HLA Antigens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand