Cellular immunity is strongly implicated in control of CMV disease; however, many mechanistic details remain unresolved. We previously demonstrated T cell activation responses to CMV-infected allogeneic endothelial cells (EC), suggesting EC as a mediator of CMV response in the transplant recipient. We now test the hypothesis that CMV-specific T cell responses can be directly stimulated by infected EC in an environment free of potentially confounding allogeneic factors. By isolating splenic 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 demonstrated significantly enhanced responses by CMV-seropositive donor-derived T cells cocultured with CMV- infected GVEC, as compared with those 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 minimal, regardless of CMV status of stimulator GVEC. Intriguingly, CD4 responses were observed in spite of the fact that CMV-infected EC express no HLA class II. Finally, attenuation of CMV- stimulated T cell proliferation observed in the presence of blocking Ab specific for ICAM-1 suggests a contributing role for CMV-enhanced endothelial ICAM-1 expression in the activation response. These studies demonstrate that EC can stimulate autologous T cell responses to CMV in the absence of accessory APC and suggest potentially novel mechanisms of immune activation.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - Apr 1 1998|
ASJC Scopus subject areas
- Immunology and Allergy