Effects of cytomegalovirus infection and prolonged cold ischemia on chronic rejection of rat renal allografts

Previous studies have demonstrated that both cytomegalovirus (CMV) infectio n and prolonged cold ischemia of the allograft (CI) are associated with chr onic rejection of renal transplants. The purpose of this study is to invest igate the effect of CMV infection, of CI and of the combination of both, on the progression of chronic rejection, and to obtain a more detailed insigh t in their effects on the expression of adhesion molecules. Therefore, a ra t transplantation model was used. Lewis recipients of renal allografts (wit h and without CI) from MHC-incompatible Brown Norway rats were inoculated w ith rat CMV or left uninfected. CMV infection alone resulted in an increase d influx of CD4+ cells and macrophages early after infection, and in an inc rease in glomerular sclerosis and intima proliferation. CI caused an increa se in infiltrating NK cells and an effect on intimal proliferation, glomeru lar sclerosis, and tubular atrophy. When CMV infection and CI were combined . an additive effect could be measured. This was however not the case for t he function of the kidney. The creatinin showed a synergistic effect of the two influencing factors. Due to the CMV infection, an increase in CD49 d c ells was detected. CI resulted in an increase in CD18 cells and an increase in the expression of CD62P on vessels, and CD54 and CD44 on tubules, When CMV infection and CI were combined, all the effects caused by CMV and CI al one were present in an additional way. The results of the present study suggest that special attention should be p aid to the recipient of an ischemically injured graft when either the donor or the recipient is CMV-infected. The patterns seen in histology, the infi ltration of leukocytes and the expression of adhesion molecules, suggest th at CI and CMV infection both have an effect on rejection, but act by differ ent mechanisms.