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Bcl-2 Transduction Protects Human Endothelial Cell Synthetic Microvessel Grafts from Allogeneic T Cells In Vivo¹

Lian Zheng^*, Thomas F. Gibson^*, Jeffrey S. Schechner^,, Jordan S. Pober^*,, and Alfred L. M. Bothwell^2,*,

^* Section of Immunobiology and Interdepartmental Program in Vascular Biology and Transplantation, Departments of Dermatology and Pathology, Yale University School of Medicine, New Haven, CT 06520

T cell interactions with vascular endothelial cells (EC) are of central importance for immune surveillance of microbes and for pathological processes such as atherosclerosis, allograft rejection, and vasculitis. Animal (especially rodent) models incompletely predict human immune responses, in particular with regard to the immunological functions of EC, and in vitro models may not accurately reflect in vivo findings. In this study, we describe the development of an immunodeficient SCID/bg murine model combining a transplanted human synthetic microvascular bed with adoptive transfer of human T lymphocytes allogeneic to the cells of the graft that more fully recapitulates T cell responses in natural tissues. Using this model, we demonstrate that transduced Bcl-2 protein in the engrafted EC effectively prevents injury even as it enhances T cell graft infiltration and replication.

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