Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation

Journal Article · Mon May 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.9.3306· OSTI ID:5560224

Ikehara, S; Yasumizu, R; Inaba, M; Izui, S; Hayakawa, K; Sekita, K; Toki, J; Sugiura, K; Iwai, H; Nakamura, T ^[1]

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1. Kansai Medical Univ., Osaka (Japan)

Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB x 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 greater than 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 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 In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells.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, resids in abnormalities present in stem cells.

• OSTI ID: 5560224
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:9; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BONE MARROW
TRANSPLANTS
STEM CELLS
RADIOSENSITIVITY
UROGENITAL SYSTEM DISEASES
PATHOGENESIS
ANTIGENS
BIOLOGICAL RADIATION EFFECTS
COMPLEMENT
IMMUNE SYSTEM DISEASES
KIDNEYS
LYMPHOCYTES
MICE
RADIATION CHIMERAS
WHOLE-BODY IRRADIATION
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
EXTERNAL IRRADIATION
HEMATOPOIETIC SYSTEM
IRRADIATION
LEUKOCYTES
MAMMALS
MATERIALS
MOSAICISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIATION EFFECTS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals