Lymphocytes induce enhanced expression of HLA class I antigens on cytomegalovirus-infected syngeneic human endothelial cells

Human cytomegalovirus (HCMV) infection has been associated with enhanced expression of HLA antigens on the endothelium and with cellular infiltrates within the graft following human organ transplantation. We investigated the interactions between human cytomegalovirus-infected cultured endothelial cells and cocultured syngeneic as well as allogeneic lymphocytes. Our objective was to find out whether cocultured lymphocytes elicit HCMV-mediated immune responses. In this report we focus on the modified expression of HLA antigens on the surface membrane of human umbilical vein endothelial cells (HUVECs). Endothelial expression of HLA class I and II antigens was measured by means of flow cytometry. Cocultures of HCMV-infected HUVECs with unprimed autologous PBLs led to virus-specific lymphocyte response, resulting in enhanced expression of HLA class I on HUVECs, This effect was only observed when lymphocytes were added to HUVECs during the very early phase after virus inoculation and was due to the stimulation of the CD8+ T-cell subpopulation. The modification of endothelial HLA expression was not observed in transwell cocultures, indicating the importance of cellular contact between endothelial cells and lymphocytes to elicit this effect. We conclude that HCMV-infected endothelial cells may induce virus-specific responses of unprimed syngeneic lymphocytes that lead to upregulated HLA class I expression on the endothelium. This pathway might be of important relevance for graft rejection crises after transplantation.