Immunophenotype of vascular rejection in renal transplants.

Understanding of the pathogenesis of vascular rejection processes encountered in renal transplants is limited. Although initially and still widely thought to be antibody mediated, it is commonly difficult to demonstrate deposition of immunoglobulin (Ig) in affected arteries. We studied the vascular lesions present in 22 transplanted human kidneys with a panel of antibodies and lectins to evaluate the presence of granulocytes (Leu M1), leukocytes (anti-CD45), B cells (L26), T cells (UCHL-1), monocyte/macrophages (HAM 56), endothelial proliferation (Ulex I factor VIII-related antigen), and smooth muscle proliferation (HHF 35). Active (cellular) vascular rejection showed intimal infiltration of T lymphocytes and monocytes/macrophages (Mac) but not B lymphocytes. Lesions of greater chronicity (reduction in cellularity, increase in intimal stromal matrix) showed progressive diminution of the T cell infiltrate but persistence of Mac accompanied by increased smooth muscle cells. Endothelial alterations were limited to disruption and lifting from supporting stroma by infiltrating inflammatory cells; proliferative changes as detected by increased numbers of cells binding Ulex I were not identified. The cell infiltrates were similar in large (renal artery) and small (interlobular) arteries. Evidence for specific deposition of Ig was not present in cases studied by immunofluorescence studies. These studies suggest vascular rejection is commonly mediated by cellular immune mechanisms and the general supposition equating vascular rejection occurring beyond the peritransplant period with humoral rejection is mistaken. Persistent Mac in chronic lesions may be limited to scavenger functions, but their presence suggests activity in modulating intimal proliferation analogous to current hypotheses for such a role for Mac in atherosclerosis.