Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes

J Clin Invest. 2003 May;111(9):1357-63. doi: 10.1172/JCI15995.


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 beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunization
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Lymphocyte Subsets
  • Mice
  • Mice, Inbred NOD
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Proinsulin / genetics
  • Proinsulin / immunology*
  • Proinsulin / metabolism
  • Spleen / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transplantation, Isogeneic


  • Autoantigens
  • Ovalbumin
  • Proinsulin