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 , marandil@tbzmed.ac.ir
Abstract: (4932 Views)
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.