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. 1979 Aug 1;150(2):371–378. doi: 10.1084/jem.150.2.371

Reversal of nzb/nzw disease with total lymphoid irradiation

PMCID: PMC2185621  PMID: 313431

Abstract

NZB/NZW mice spontaneously exhibit autoimmune disease similar to that seen in human systemic lupus erythematosus (SLE). We demonstrated that total lymphoid irradiation (TLI) reversed well expressed disease in 6- mo-old NZB/NZW females with a prolongation in survival, decrease in proteinuria, and decrease in anti-DNA antibodies as compared to control animals. Few side effects were observed in the treated group. TLI also prolonged survival in animals with advanced renal disease. These findings suggest that TLI may have application to the treatment of human SLE.

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Selected References

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

  1. Casey T. P. Immunosuppression by cyclophosphamide in NZB X NZW mice with lupus nephritis. Blood. 1968 Sep;32(3):436–444. [PubMed] [Google Scholar]
  2. Coleman C. N., Williams C. J., Flint A., Glatstein E. J., Rosenberg S. A., Kaplan H. S. Hematologic neoplasia in patients treated for Hodgkin's disease. N Engl J Med. 1977 Dec 8;297(23):1249–1252. doi: 10.1056/NEJM197712082972303. [DOI] [PubMed] [Google Scholar]
  3. Fuks Z., Strober S., Bobrove A. M., Sasazuki T., McMichael A., Kaplan H. S. Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease. J Clin Invest. 1976 Oct;58(4):803–814. doi: 10.1172/JCI108532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gelfand M. C., Steinberg A. D., Nagle R., Knepshield J. H. Therapeutic studies in NZB-W mice. I. Synergy of azathioprine, cyclophosphamide and methylprednisolone in combination. Arthritis Rheum. 1972 May-Jun;15(3):239–246. doi: 10.1002/art.1780150304. [DOI] [PubMed] [Google Scholar]
  5. Gelfand M. C., Steinberg A. D. Therapeutic studies in NZB-W mice. II. Relative efficacy of azathioprine, cyclophosphamide and methylprednisolone. Arthritis Rheum. 1972 May-Jun;15(3):247–252. doi: 10.1002/art.1780150305. [DOI] [PubMed] [Google Scholar]
  6. Hahn B. H., Bagby M. K., Hamilton T. R., Osterland C. K. Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in NZP-NZW mice. Arthritis Rheum. 1973 Mar-Apr;16(2):163–170. doi: 10.1002/art.1780160205. [DOI] [PubMed] [Google Scholar]
  7. Hahn B. H., Knotts L., Ng M., Hamilton T. R. Influence of cyclophosphamide and other immunosuppressive drugs on immune disorders and neoplasia in NZB/NZW mice. Arthritis Rheum. 1975 Mar-Apr;18(2):145–152. doi: 10.1002/art.1780180212. [DOI] [PubMed] [Google Scholar]
  8. Horowitz R. E., Dubois E. L., Weiner J., Strain L. Cyclophosphamide treatment of mouse systemic lupus erythematosus. Lab Invest. 1969 Sep;21(3):199–206. [PubMed] [Google Scholar]
  9. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  10. Klassen L. W., Budman D. R., Williams G. W., Steinberg A. D., Gerber N. L. Ribavirin: efficacy in the treatment of murine autoimmune disease. Science. 1977 Feb 25;195(4280):787–789. doi: 10.1126/science.299957. [DOI] [PubMed] [Google Scholar]
  11. Krakauer R. S., Waldmann T. A., Strober W. Loss of suppressor T cells in adult NZB/NZW mice. J Exp Med. 1976 Sep 1;144(3):662–673. doi: 10.1084/jem.144.3.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lehman D. H., Wilson C. B., Dixon F. J. Increased survival times of New Zealand hybrid mice immunosuppressed by graft-versus-host reactions. Clin Exp Immunol. 1976 Aug;25(2):297–302. [PMC free article] [PubMed] [Google Scholar]
  14. Morris A. D., Esterly J., Chase G., Sharp G. C. Cyclophosphamide protection in NZB/NZW disease. Mechanisms and therapeutic regimens. Arthritis Rheum. 1976 Jan-Feb;19(1):49–55. doi: 10.1002/art.1780190108. [DOI] [PubMed] [Google Scholar]
  15. Moutsopoulos H. M., Boehm-Truitt M., Kassan S. S., Chused T. M. Demonstration of activation of B lymphocytes in New Zealand black mice at birth by an immunoradiometric assay for murine IgM. J Immunol. 1977 Nov;119(5):1639–1644. [PubMed] [Google Scholar]
  16. Russell P. J., Hicks J. D. Cyclophosphamide treatment of renal disease in (NZB x NZW) F1 hybrid mice. Lancet. 1968 Mar 2;1(7540):440–441. doi: 10.1016/s0140-6736(68)92778-5. [DOI] [PubMed] [Google Scholar]
  17. Slavin S., Gottlieb M., Strober S., Bieber C., Hoppe R., Kaplan H. S., Grumet F. C. Transplantation of bone marrow in outbred dogs without graft-versus-host disease using total lymphoid irradiation. Transplantation. 1979 Feb;27(2):139–142. [PubMed] [Google Scholar]
  18. Slavin S., Reitz B., Bieber C. P., Kaplan H. S., Strober S. Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts. J Exp Med. 1978 Mar 1;147(3):700–707. doi: 10.1084/jem.147.3.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Slavin S., Strober S., Fuks Z., Kaplan H. S. Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts. J Exp Med. 1977 Jul 1;146(1):34–48. doi: 10.1084/jem.146.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Slavin S., Strober S., Fuks Z., Kaplan H. S. Use of total lymphoid irradiation in tissue transplantation in mice. Transplant Proc. 1977 Mar;9(1):1001–1004. [PubMed] [Google Scholar]
  21. Staples P. J., Talal N. Relative inability to induce tolerance in adult NZB and NZB-NZW F1 mice. J Exp Med. 1969 Jan 1;129(1):123–139. doi: 10.1084/jem.129.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steinberg A. D., Gelfand M. C., Hardin J. A., Lowenthal D. T. Therapeutic studies in NZB/W mice. III. Relationship between renal status and efficacy of immunosuppressive drug therapy. Arthritis Rheum. 1975 Jan-Feb;18(1):9–14. doi: 10.1002/art.1780180102. [DOI] [PubMed] [Google Scholar]
  23. Steinberg A. D. Pathogenesis of autoimmunity in New Zealand mice. V. Loss of thymic suppressor function. Arthritis Rheum. 1974 Jan-Feb;17(1):11–14. doi: 10.1002/art.1780170103. [DOI] [PubMed] [Google Scholar]
  24. Steinberg A. D., Pincus T., Talal N. DNA-binding assay for detection of anti-DNA antibodies in NZB-NZW F1 mice. J Immunol. 1969 Mar;102(3):788–790. [PubMed] [Google Scholar]
  25. Walker S. E., Bole G. G., Jr Augmented incidence of neoplasia in NZB-NZW mice treated with long-term cyclophosphamide. J Lab Clin Med. 1973 Oct;82(4):619–633. [PubMed] [Google Scholar]
  26. Zan-Bar I., Slavin S., Strober S. Induction and mechanism of tolerance to bovine serum albumin in mice given total lymphoid irradiation (TLI). J Immunol. 1978 Oct;121(4):1400–1404. [PubMed] [Google Scholar]

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