Human Fibroblasts Transfected with Cytomegalovirus Immediate-Early Genes Show Increased MHC Class I Expression and Are Targets for Natural Killer Cell-Mediated Cytotoxicity

Abstract

Natural killer (NK) cells are an important line of defense against viral infections, such as those caused by cytomegalovirus (CMV), but in the context of solid organ transplantation NK responses to CMV-infected graft cells might be deleterious to the graft survival. To gain a better understanding of NK responses to CMV-infected human lung fibroblasts (HLF), we transfected HLF with a plasmid expressing CMV immediate-early(IE) genes under the control of the CMV major IE promoter and compared major histocompatibility complex (MHC) class I expression and NK-mediated lysis of transfected cells, CMV-infected cells, and appropriate controls. HLF transfected with CMV IE genes showed increased MHC Class I expression and triggered NK-mediated cytotoxicity at the same level as CMV-infected HLF and at significantly higher levels than mock-infected or mock-transfected controls. Transfection of CMV genes provides an experimental model for molecular studies of CMV- and allograft-specific cell-mediated immunity and modulation.