Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 May;86(9):3306–3310. doi: 10.1073/pnas.86.9.3306

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

S Ikehara 1, R Yasumizu 1, M Inaba 1, S Izui 1, K Hayakawa 1, K Sekita 1, J Toki 1, K Sugiura 1, H Iwai 1, T Nakamura 1, et al.
PMCID: PMC287120  PMID: 2654943

Abstract

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 In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells.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.

Full text

PDF
3306

Images in this article

3307Image
on p.3307
3307Image
on p.3307
3307Image
on p.3307
3307Image
on p.3307
3307Image
on p.3307
3307Image
on p.3307

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akizuki M., Reeves J. P., Steinberg A. D. Expression of autoimmunity by NZB/NZW marrow. Clin Immunol Immunopathol. 1978 Jul;10(3):247–250. doi: 10.1016/0090-1229(78)90177-0. [DOI] [PubMed] [Google Scholar]
  2. Fujiwara M., Kariyone A. One-way occurrence of graft-versus-host disease in bone marrow chimaeras between congenic MRL mice. Immunology. 1984 Oct;53(2):251–256. [PMC free article] [PubMed] [Google Scholar]
  3. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  4. Hayakawa K., Hardy R. R., Herzenberg L. A. Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression. Eur J Immunol. 1986 Apr;16(4):450–456. doi: 10.1002/eji.1830160423. [DOI] [PubMed] [Google Scholar]
  5. Hayakawa K., Hardy R. R., Parks D. R., Herzenberg L. A. The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. J Exp Med. 1983 Jan 1;157(1):202–218. doi: 10.1084/jem.157.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ikehara S., Good R. A., Nakamura T., Sekita K., Inoue S., Oo M. M., Muso E., Ogawa K., Hamashima Y. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2483–2487. doi: 10.1073/pnas.82.8.2483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Izui S., McConahey P. J., Theofilopoulos A. N., Dixon F. J. Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus. J Exp Med. 1979 May 1;149(5):1099–1116. doi: 10.1084/jem.149.5.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jyonouchi H., Kincade P. W., Good R. A., Fernandes G. Reciprocal transfer of abnormalities in clonable B lymphocytes and myeloid progenitors between NZB and DBA/2 mice. J Immunol. 1981 Sep;127(3):1232–1235. [PubMed] [Google Scholar]
  9. Maruyama N., Furukawa F., Nakai Y., Sasaki Y., Ohta K., Ozaki S., Hirose S., Shirai T. Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in (NZB X NZW)F1 hybrid and the correlation to renal disease. J Immunol. 1983 Feb;130(2):740–746. [PubMed] [Google Scholar]
  10. Morse H. C., 3rd, Davidson W. F., Yetter R. A., Murphy E. D., Roths J. B., Coffman R. L. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol. 1982 Dec;129(6):2612–2615. [PubMed] [Google Scholar]
  11. Morton J. I., Siegel B. V. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2162–2165. doi: 10.1073/pnas.71.6.2162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nakamura T., Good R. A., Yasumizu R., Inoue S., Oo M. M., Hamashima Y., Ikehara S. Successful liver allografts in mice by combination with allogeneic bone marrow transplantation. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4529–4532. doi: 10.1073/pnas.83.12.4529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakamura T., Ikehara S., Good R. A., Inoe S., Sekita K., Furukawa F., Tanaka H., Oo M. M., Hamashima Y. Abnormal stem cells in autoimmune-prone mice are responsible for premature thymic involution. Thymus. 1985;7(3):151–160. [PubMed] [Google Scholar]
  14. Perkins D. L., Michaelson J., Marshak-Rothstein A. The lpr gene is associated with resistance to engraftment by lymphoid but not erythroid stem cells from normal mice. J Immunol. 1987 Jan 15;138(2):466–469. [PubMed] [Google Scholar]
  15. Theofilopoulos A. N., Balderas R. S., Gozes Y., Aguado M. T., Hang L. M., Morrow P. R., Dixon F. J. Association of lpr gene with graft-vs.-host disease-like syndrome. J Exp Med. 1985 Jul 1;162(1):1–18. doi: 10.1084/jem.162.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES