TY - JOUR
T1 - An in vitro model of T cell activation by autologous cytomegalovirus (CMV)-infected human adult endothelial cells
T2 - Contribution of CMV-enhanced endothelial ICAM-1
AU - Waldman, W. James
AU - Knight, Deborah A.
AU - Huang, Emina H.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9531269
AN - SCOPUS:0032055859
SN - 0022-1767
VL - 160
SP - 3143
EP - 3151
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -