Prolonged survival of pancreatic islet allografts mediated by adenovirus immunoregulatory transgenes

Shimon Efrat, Gyorgy Fejer, Michael Brownlee, Marshall S. Horwitz

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The adenovirus (Ad) early region 3 (E3) genes code for at least four proteins that inhibit the host immune responses mediated by cytotoxic T lymphocytes and tumor necrosis factor α. To evaluate the potential use of these immunoregulatory viral functions in facilitating allogeneic cell transplantation, the Ad E3 genes were expressed in pancreatic beta cells in transgenic mice under control of the rat insulin II promoter. Transgenic H- 2(b/d) (C57BL/6 x BALB/c) islets, expressing the Ad E3 genes, remained viable for at least 94 days after transplantation under the kidney capsule of BALB/c (H-2(d)) recipients. Nontransgenic H-2(b/d) control islets were rejected as anticipated between 14 and 28 days. Histological analysis of the transplanted transgenic islets revealed normal architecture. Immunohistochemical studies with antisera to islet hormones revealed the presence of both β and non-β islet cells, suggesting a propagation of the immunosuppressive effect of Ad proteins from β cells to other islet cells. The use of viral genes, which have evolved to regulate virus-host interactions, to immunosupress the antigenicity of donor transplant tissue suggests additional ways for prolonging allograft survival. In addition, these findings have implications for designing Ad vectors for gene therapy.

Original languageEnglish (US)
Pages (from-to)6947-6951
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number15
DOIs
Publication statusPublished - Jul 18 1995

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Keywords

  • diabetes
  • major histocompatibility complex
  • transplantation
  • tumor necrosis factor

ASJC Scopus subject areas

  • General

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