AN IN-VITRO MODEL OF T-CELL ACTIVATION BY AUTOLOGOUS CYTOMEGALOVIRUS (CMV)-INFECTED HUMAN ADULT ENDOTHELIAL-CELLS - CONTRIBUTION OF CMV-ENHANCED ENDOTHELIAL ICAM-1

Cellular immunity is strongly implicated in control of CMV disease; ho wever, many mechanistic details remain unresolved. We previously demon strated T cell activation responses to CMV-infected allogeneic endothe lial cells (EC), suggesting EC as a mediator of CMV response in the tr ansplant recipient, We now test the hypothesis that CMV-specific T cel l responses can be directly stimulated by infected EC in an environmen t free of potentially confounding allogeneic factors. By isolating spl enic T cells and gonadal vein endothelial cells (GVEC) from individual cadaveric organ donors, we have developed an in vitro model of T cell interaction with autologous CMV-infected EC. Proliferation assays dem onstrated significantly enhanced responses by CMV-seropositive donor-d erived T cells cocultured with CMV-infected GVEC, as compared with tho se elicited by uninfected cells. Similarly, as determined by limiting dilution analysis of IL-2-producing cells, T cell response frequencies to infected GVEC were significantly greater than to uninfected EC. In contrast, responses of CMV-seronegative donor-derived T cells were mi nimal, regardless of CMV status of stimulator GVEC. Intriguingly, CD4 responses were observed in spite of the fact that CMV-infected EC expr ess no HLA class II. Finally, attenuation of CMV-stimulated T cell pro liferation observed in the presence of blocking Ab specific for ICAM-1 suggests a contributing role for CMV-enhanced endothelial ICAM-1 expr ession in the activation response. These studies demonstrate that EC c an stimulate autologous T cell responses to CMV in the absence of acce ssory APC and suggest potentially novel mechanisms of immune activatio n.