Open AccessLong-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation.
Author(s) -
Susumu Ikehara,
Ryoji Yasumizu,
Muneo Inaba,
Shozo Izui,
Kyoko Hayakawa,
Kenichi Sekita,
Junko Toki,
Kikuya Sugiura,
Hiroshi Iwai,
Toshio Nakamura
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.9.3306
Subject(s) - autoimmune disease , immunology , bone marrow , transplantation , autoimmunity , medicine , histocompatibility , minor histocompatibility antigen , disease , serology , major histocompatibility complex , immune system , antibody , antigen , human leukocyte antigen
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 In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells.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, residues in abnormalities present in stem cells.