Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes
- Author(s)
- Steptoe, RJ; Ritchie, JM; Harrison, LC;
- Details
- Publication Year 2003-05,Volume 111,Issue #9,Page 1357-1363
- Journal Title
- JOURNAL OF CLINICAL INVESTIGATION
- Publication Type
- Journal Article
- 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 P 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.
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Keywords
- GLUTAMIC-ACID DECARBOXYLASE; ANTIGEN-PRESENTING CELLS; BONE-MARROW TRANSPLANTATION; DENDRITIC CELLS; NOD MICE; IN-VIVO; T-CELLS; B-CELLS; INSULIN; TOLERANCE
- Publisher's Version
- https://doi.org/10.1172/JCI200315995
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-05-01 12:00:00