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Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes
Raymond J. Steptoe, … , Janine M. Ritchie, Leonard C. Harrison
Raymond J. Steptoe, … , Janine M. Ritchie, Leonard C. Harrison
Published May 1, 2003
Citation Information: J Clin Invest. 2003;111(9):1357-1363. https://doi.org/10.1172/JCI15995.
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Article Metabolism

Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes

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Abstract

Bone marrow or hematopoietic stem cell transplantation is a potential treatment for autoimmune disease. The clinical application of this approach is, however, limited by the risks associated with allogeneic transplantation. In contrast, syngeneic transplantation would be safe and have wide clinical application. Because T cell tolerance can be induced by presenting antigen on resting antigen-presenting cells (APCs), we reasoned that hematopoietic stem cells engineered to express autoantigen in resting APCs could be used to prevent autoimmune disease. Proinsulin is a major autoantigen associated with pancreatic β cell destruction in humans with type 1 diabetes (T1D) and in autoimmune NOD mice. Here, we demonstrate that syngeneic transplantation of hematopoietic stem cells encoding proinsulin transgenically targeted to APCs totally prevents the development of spontaneous autoimmune diabetes in NOD mice. This antigen-specific immunotherapeutic strategy could be applied to prevent T1D and other autoimmune diseases in humans.

Authors

Raymond J. Steptoe, Janine M. Ritchie, Leonard C. Harrison

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