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

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 partic...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-09, Vol.173 (5), p.3020-3026
Main Authors: Zheng, Lian, Gibson, Thomas F, Schechner, Jeffrey S, Pober, Jordan S, Bothwell, Alfred L. M
Format: Article
Language:English
Subjects:
Animals
Blood Vessels
Endothelial Cells - immunology
Endothelial Cells - physiology
Endothelium, Vascular - immunology
Endothelium, Vascular - physiology
Humans
Mice
Mice, SCID
Prostheses and Implants
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - immunology
Proto-Oncogene Proteins c-bcl-2 - physiology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.5.3020