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Published on: May 6, 2013
Inducing Specific Immune Tolerance to Prevent Type 1 Diabetes in NOD Mice
Fang Liu1, Zhong Yao, Qibin Jiao
1From the *Department of Radiology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, China; †Donnellyl Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada; ‡Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Institute of Ageing Research, School of Medicine, Hangzhou Normal University, Hangzhou; and §Department of Vascular Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, China.
Objectives:
Proinsulin is the first autoantigen in type 1 diabetes (T1D). We reasoned that coupling hematopoietic stem cells (HSCs) transplantation with ex vivo transduction of syngeneic HSCs with lentiviral vectors to express proinsulin II could prevent T1D in nonobese diabetic (NOD) mice.
Methods:
Hematopoietic stem cells were isolated from 6- to 8-week-old NOD female mice and transduced in vitro with lentiviral vectors encoding proinsulin II. Preconditioned 3- to 4-week-old female NOD mice were transplanted with transduced or nontransduced HSCs and compared with age-matched unmanipulated control. The insulitis, T1D development, and immune reconstitution were assessed.
Results:
The mean (SD) insulitis score was significantly reduced (1.156 [0.575] vs 2.156 [0.892] or 3.043 [0.728], P = 0.009 or <0.001), and diabetes was nearly completely prevented (1/13 vs 5/12 or 4/9, P = 0.031 or 0.013) in recipients of transduced HSCs expressing proinsulin II as compared with recipients of nontransduced HSCs or unmanipulated control. Sialitis, reconstitution of peripheral blood leukocytes, and in vitro recall responses to ovalbumin were not different between 3 groups of mice.
Conclusions:
Syngeneic transplantation of HSCs transduced ex vivo with lentiviral vectors to encode proinsulin II is a novel strategy to prevent T1D.
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