title: Stem cells engineered to express self-antigen to treat autoimmunity.
abstract: Autoimmune diseases are incurable. We propose a combination curative strategy using haematopoietic stem cells and gene therapy. The strategy should establish molecular chimerism with culprit antigen expressed by donor antigen-presenting cells in the thymus, resulting in immunological tolerance. Our strategy is based on the intrathymic tolerance and disease resistance established by transgenic expression of antigen in the thymus under control of an MHC class II promoter. We propose that transplantation with genetically engineered stem cells provides an advance over current autologous bone marrow transplantation, in that it should remove the significant risk of disease relapse.
authors.affiliation: Department of Pathology and Immunology, Monash University Medical School, Victoria 3181, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Alderuccio
authors.forename: Kim
authors.initials: K
authors.lastname: Murphy
authors.forename: Ban-Hock
authors.initials: BH
authors.lastname: Toh
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy*; D016026:Bone Marrow Transplantation; D002678:Chimera / Q000276:immunology; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D017634:Self Tolerance / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D001324:Autoantigens