Long-Term Observations of Autoimmune-Prone Mice Treated for Autoimmune Disease by Allogeneic Bone Marrow Transplantation

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-05, Vol.86 (9), p.3306-3310
• Main Authors: Ikehara, Susumu, Yasumizu, Ryoji, Inaba, Muneo, Izui, Shozo, Hayakawa, Kyoko, Sekita, Ken'Ichi, Toki, Junko, Sugiura, Kikuya, Iwai, Hiroshi, Nakamura, Takao, Muso, Eri, Hamashima, Yoshihiro, Good, Robert A.
• Format: Article
• Language: English
• Subjects: 560152 - Radiation Effects on Animals- Animals; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; ANTIGENS; Antigens, Ly - analysis; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmune Diseases - therapy; B lymphocytes; B-Lymphocytes - immunology; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOLOGICAL MATERIALS; BIOLOGICAL RADIATION EFFECTS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; BONE MARROW; Bone Marrow - immunology; Bone Marrow - radiation effects; Bone Marrow Transplantation; Chimera; CHIMERAS; COMPLEMENT; Complement C3 - analysis; CONNECTIVE TISSUE CELLS; Cytotoxicity Tests, Immunologic; DISEASES; EXTERNAL IRRADIATION; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HEMATOPOIETIC SYSTEM; IMMUNE SYSTEM DISEASES; Immunoglobulin G - analysis; Interleukin-2 - biosynthesis; IRRADIATION; Kidney - immunology; Kidney - pathology; KIDNEYS; Lesions; LEUKOCYTES; LYMPHOCYTES; Male; MAMMALS; MATERIALS; MICE; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred NZB; Mice, Nude; MOSAICISM; ORGANIC COMPOUNDS; ORGANS; PATHOGENESIS; PROTEINS; RADIATION CHIMERAS; Radiation dosage; RADIATION EFFECTS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIOSENSITIVITY; Recurrence; RODENTS; SOMATIC CELLS; Spleen cells; STEM CELLS; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; Tissue, organ and graft immunology; TISSUES; Transplantation immunology; TRANSPLANTS; UROGENITAL SYSTEM DISEASES; VERTEBRATES; WHOLE-BODY IRRADIATION
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.9.3306

Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB × NZW)F1(B/W), BXSB, and MRL/Mr-lpr-lpr (MRL/lpr) mice with established autoimmune disease at the time of ABMT. In the BXSB or B/W mice, ABMT cured all aspects of autoimmune disease. Glomerular damage, revealed by histological study was dramatically improved. Serological abnormalities and immunologic functions also were normalized. Correction of autoimmune disease and advanced renal disease in BXSB and B/W mice regularly lasted >5-6 mo and even 1 yr after ABMT. In the MRL/lpr mice, however, autoimmune and renal disease at first improved but then recurred after ABMT, apparently because of intolerance of the mice for high doses of irradiation and a high degree of resistance of recipient stem cells to irradiation. In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells. B220+Ly-1+cells, present in increased numbers in untreated MRL/lpr mice, initially returned to normal levels after ABMT but then reappeared in the MRL/lpr mice that had received marrow from donors having few such lymphocytes. Thus, our results show that MRL/lpr mice possess abnormal radioresistant stem cells and provide impressive evidence that the origin of autoimmune diseases in this strain, as in the several other strains studied, resides in abnormalities present in stem cells.