INDUCTION OF TYPE 1 DIABETES IN DIABETES-RESISTA NT (BB-DR) RATS

Authors

  • LEILI YAZDCHI -MARANDI From the *Immunology Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran,and the **Departments of Immunology and Medicine, Sunnybrook and Women s College Health Sciences Center, University of Toronto, Toronto, Ontario, Canada
  • PHILIPPE POUSSIER the Departments of Immunology and Medicine, Sunnybrook and Women s College Health Sciences Center, University of Toronto, Toronto, Ontario, Canada
  • SHEELA RAMANATHAN the Departments of Immunology and Medicine, Sunnybrook and Women s College Health Sciences Center, University of Toronto, Toronto, Ontario, Canada
Abstract:

The BioBreeding- Diabetes Prone (BB-DP) rat spontaneously develops an autoimmune diabetic syndrome that is dependent on the RT1 u Major Histocompatibility Complex (MHC) haplotype and homozygosity for an allele at the Lymphopenia (Lyp) locus. Lyp mutation is responsible for a peripheral T -lymphopenia. There are other genetic loci contributing to diabetes susceptibility in this strain. BB rats carrying wildtype Lyp alleles are not lymphopenic and are resistant to spontaneous diabetes (Diabetes R esistant [DR]). Our study shows that thymectomy and exposure to one sublethal dose of g-irradiation (TX-R) at 4 weeks of age result in the rapid development of insulitis followed by diabetes in 100% of DR rats. Administration of CD45RCCD4+ TCRcb+ T cells from unmanipulated syngeneic donors immediately after irradiation prevents the disease. Splenic T cells from TX -R induced diabetic animals adoptively transfer type 1 diabetes to T-deficient recipients. WAG, WF and LEW strains are resistant to TX -R induced insulitis/ diabetes. This novel model of TX -R induced diabetes in BB-DR rats can be used to identify environmental and cellular factors that are responsible for the initiation of antipancreatic autoimmunity.

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Journal title

volume 18  issue 4

pages  365- 370

publication date 2005-11

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