Role of cytomegalovirus infection in allograft rejection: a review of possible mechanisms

Several lines of evidence indicate that viral infections, particularly with cytomegalovirus (CMV), play a role in the pathogenesis of solid organ allograft rejection. A diagnostic feature of acute rejection is infiltration of allograft parenchyma by lymphocytes, a process regulated by induction of adhesion molecules on vascular endothelial cells and their ligands on leucocytes. Data derived from biopsies of CMV-infected transplant recipients, as well as from experimental models of transplantation, indicate that CMV infection can result in an upregulation of such adhesion molecules, thereby facilitating the inflammatory process. Infection with CMV is also associated with an increased expression of MHC class II on multiple cell types. Since recognition of nonself MHC antigens is the major determinant of allograft rejection, an upregulation of these molecules could contribute to graft failure. Infection with CMV has also been implicated in the induction of smooth muscle proliferation and intimal thickening, both hallmarks of transplant atherosclerosis, which constitutes the most common cause of heart allograft failure. CMV can be classified into four, possibly five, different genotypes based on restriction length polymorphism of the envelope glycoprotein B gene; these genotypes may exhibit varied geographic and demographic frequency distributions and also differ in their pathogenicity and cell tropism. Further studies are needed to evaluate these issues and in particular the genetic contribution of the recipient to CMV modulation of rejection.