An in vitro model of T cell activation by autologous cytomegalovirus (CMV)-infected human adult endothelial cells: Contribution of CMV-enhanced endothelial ICAM-1

W. James Waldman, Deborah A. Knight, Emina H. Huang

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish (US)
Pages (from-to)3143-3151
Number of pages9
JournalJournal of Immunology
Volume160
Issue number7
StatePublished - Apr 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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