Persistence of recipient lymphocytes in NOD mice after irradiation and bone marrow transplantation.
The non-obese diabetic (NOD) mouse is a unique and invaluable model of autoimmune disease, in particular type 1 diabetes. Bone marrow transplantation as a therapy for type 1 diabetes has been explored in NOD mice. NOD mice require higher doses of conditioning irradiation for successful allogeneic bone marrow transplantation, suggesting that NOD hematopoietic cells are radioresistant compared to those of other mouse strains. However, studies of hematopoietic reconstitution in NOD mice are hampered by the lack of mice bearing a suitable cell-surface marker that would allow transferred cells or their progeny to be distinguished. In order to monitor hematopoietic reconstitution in NOD mice we generated congenic NOD mice that carry the alternative allelic form of the pan-leukocyte alloantigen CD45. Following irradiation and congenic bone marrow transplantation, we found that the myeloid lineage was rapidly reconstituted by cells of donor origin but substantial numbers of recipient T lymphocytes persisted even after supra-lethal irradiation. This indicates that radiation resistance in the NOD hematopoietic compartment is a property primarily of mature T lymphocytes.
Steptoe
Raymond J
RJ
Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Victoria, Australia. steptoe@wehi.edu.au
Stankovic
Sanda
S
Lopaticki
Sash
S
Jones
Lynelle K
LK
Harrison
Leonard C
LC
Morahan
Grant
G
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D016688:Mice, Inbred NOD; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D011828:Radiation Chimera; D011836:Radiation Tolerance / Q000276:immunology; D019172:Transplantation Conditioning
D007519:Isoantigens; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1