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PMID: 7624350 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Prolonged survival of pancreatic islet allografts mediated by adenovirus immunoregulatory transgenes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 15 ·1995-07-18 ·Pages 6947-51

Efrat S, Fejer G, Brownlee M, Horwitz MS

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 alpha. 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-2b/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-2d) recipients. Nontransgenic H-2b/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 beta and non-beta islet cells, suggesting a propagation of the immunosuppressive effect of Ad proteins from beta cells to other islet cells. The use of viral genes, which have evolved to regulate virus-host interactions, to immunosupress the anti-genicity of donor transplant tissue suggests additional ways for prolonging allograft survival. In addition, these findings have implications for designing Ad vectors for gene therapy.

MeSH Terms
Adenovirus E3 Proteins/genetics,immunology Adenoviruses, Human/genetics,immunology Animals Graft Enhancement, Immunologic/methods Graft Rejection/genetics,immunology Graft Survival/genetics,immunology Immunohistochemistry Insulinoma Islets of Langerhans/cytology Islets of Langerhans Transplantation/immunology Kidney/surgery Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Transplantation, Homologous Tumor Cells, Cultured
Chemicals
Adenovirus E3 Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Efrat S
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Fejer G
Brownlee M
Horwitz M S
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44 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.15.6947
Published
1995-07-18
Pages
6947-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41448
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.15.6947 PMC Full Text View journal details
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