(Journal Article): A Single Treatment with IL-4 via Retrovirally Transduced Lymphocytes Partially Protects Against Diabetes in BioBreeding (BB) Rats
 
Zipris D, Karnieli E (The Institute of Endocrinology, Diabetes, and Metabolism, Rambam Medical Center. B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology. Haifa, Israel, eddy@tx.technion.ac.il )
 
IN: JOP. J Pancreas (Online) 2002; 03(3):76-82

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ABSTRACT: CONTEXT: Type 1 diabetes mellitus is a T cell mediated autoimmune disease with no known methods of prevention. The BioBreeding rat is used as an animal model for the study of human Type 1 diabetes. In spite of a severe lymphopenia, these animals develop spontaneous diabetes at the age of 10-12 weeks. OBJECTIVE: To examine whether anti-inflammatory gene therapy could be used to prevent autoimmune diabetes in the BioBreeding rat. DESIGN: A retroviral DNA vector, MSCVneo.IL-4, carrying the DNA sequence encoding the rat interleukin-4, was designed to transfer interleukin-4 to BioBreeding rats. Spleen cells of prediabetic animals were activated and transduced in vitro with replication-defective retroviruses expressing the MSCVneo.IL-4 vector. These lymphocytes were subsequently administered intraperitoneally to 3-4 week old prediabetic BioBreeding rats. Control animals were reconstituted with spleen cells transduced with MSCVneo vector. RESULTS: The neo gene marker was detectable by RT-PCR in rat spleen cells of up to 6 to 12 months after treatment. Fifty percent (6 out of 12) of the animals treated were protected from autoimmune disease development. CONCLUSION: Our results suggest that the BioBreeding rat can be used as a useful model to develop gene therapy regimens for diabetes. These studies provide further support for the hypothesis that interleukin-4 based gene therapy may have potential clinical value for preventing autoimmune diabetes in humans.

TYPE OF PUBLICATION: Original Article