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. 1986 Oct 1;164(4):1145–1159. doi: 10.1084/jem.164.4.1145

Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells

PMCID: PMC2188403  PMID: 3531381

Abstract

Diabetes-prone BioBreeding/Worcester (BB/Wor) rats received thrice weekly injections of mAb against antigens expressed on the surface of all T cells (OX19), cytotoxic/suppressor, and NK cells (OX8), helper/inducer cells (W3/25, OX35, OX38), and Ia+ cells (OX6, 3JP, OX17). Treatment with OX8 or OX19 achieved stable reductions of splenic and peripheral blood NK cells and helper/inducer T lymphocytes, respectively, and protected against diabetes. OX19 injections also prevented lymphocytic insulitis, thyroiditis, and the synthesis of autoantibodies to thyroid colloid and smooth muscle antigens. OX8 injections reduced splenic NK-mediated YAC-1 cell lysis, but did not prevent insulitis, thyroiditis, or autoantibody synthesis. Injections of mAb specific for antigens on the surface of helper/inducer cells, and for cells expressing IaE antigens provided marginal protection against diabetes without reductions of phenotypic subsets. These findings suggest that pancreatic beta cell destruction in the spontaneously diabetic BB/Wor rat is mediated by the combined action of NK and helper/inducer cells.

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Selected References

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  1. Alinaji, Silvers W. K., Bellgrau D., Anderson A. O., Plotkin S., Barker C. F. Prevention of diabetes in rats by bone marrow transplantation. Ann Surg. 1981 Sep;194(3):328–338. doi: 10.1097/00000658-198109000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biron C. A., Welsh R. M. Blastogenesis of natural killer cells during viral infection in vivo. J Immunol. 1982 Dec;129(6):2788–2795. [PubMed] [Google Scholar]
  3. Boitard C., Michie S., Serrurier P., Butcher G. W., Larkins A. P., McDevitt H. O. In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major histocompatibility complex gene products. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6627–6631. doi: 10.1073/pnas.82.19.6627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brideau R. J., Carter P. B., McMaster W. R., Mason D. W., Williams A. F. Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol. 1980 Aug;10(8):609–615. doi: 10.1002/eji.1830100807. [DOI] [PubMed] [Google Scholar]
  5. Brostoff S. W., Mason D. W. Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognizes T helper cells. J Immunol. 1984 Oct;133(4):1938–1942. [PubMed] [Google Scholar]
  6. Butler L., Guberski D. L., Like A. A. Genetic analysis of the BB/W diabetic rat. Can J Genet Cytol. 1983 Feb;25(1):7–15. doi: 10.1139/g83-002. [DOI] [PubMed] [Google Scholar]
  7. Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
  8. Colle E., Guttmann R. D., Seemayer T. Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex. J Exp Med. 1981 Oct 1;154(4):1237–1242. doi: 10.1084/jem.154.4.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dyrberg T., Nakhooda A. F., Baekkeskov S., Lernmark A., Poussier P., Marliss E. B. Islet cell surface antibodies and lymphocyte antibodies in the spontaneously diabetic BB Wistar rat. Diabetes. 1982 Mar;31(3):278–281. doi: 10.2337/diab.31.3.278. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Jackson R., Rassi N., Crump T., Haynes B., Eisenbarth G. S. The BB diabetic rat. Profound T-cell lymphocytopenia. Diabetes. 1981 Oct;30(10):887–889. doi: 10.2337/diab.30.10.887. [DOI] [PubMed] [Google Scholar]
  12. Jefferies W. A., Green J. R., Williams A. F. Authentic T helper CD4 (W3/25) antigen on rat peritoneal macrophages. J Exp Med. 1985 Jul 1;162(1):117–127. doi: 10.1084/jem.162.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koevary S., Rossini A., Stoller W., Chick W., Williams R. M. Passive transfer of diabetes in the BB/W rat. Science. 1983 May 13;220(4598):727–728. doi: 10.1126/science.6836309. [DOI] [PubMed] [Google Scholar]
  14. Laupacis A., Stiller C. R., Gardell C., Keown P., Dupre J., Wallace A. C., Thibert P. Cyclosporin prevents diabetes in BB Wistar rats. Lancet. 1983 Jan 1;1(8314-5):10–12. doi: 10.1016/s0140-6736(83)91558-1. [DOI] [PubMed] [Google Scholar]
  15. Like A. A., Anthony M., Guberski D. L., Rossini A. A. Spontaneous diabetes mellitus in the BB/W rat. Effects of glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes. Diabetes. 1983 Apr;32(4):326–330. doi: 10.2337/diab.32.4.326. [DOI] [PubMed] [Google Scholar]
  16. Like A. A., Appel M. C., Rossini A. A. Autoantibodies in the BB/W rat. Diabetes. 1982 Sep;31(9):816–820. doi: 10.2337/diab.31.9.816. [DOI] [PubMed] [Google Scholar]
  17. Like A. A., Dirodi V., Thomas S., Guberski D. L., Rossini A. A. Prevention of diabetes mellitus in the BB/W rat with Cyclosporin-A. Am J Pathol. 1984 Oct;117(1):92–97. [PMC free article] [PubMed] [Google Scholar]
  18. Like A. A., Kislauskis E., Williams R. R., Rossini A. A. Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat. Science. 1982 May 7;216(4546):644–646. doi: 10.1126/science.7041259. [DOI] [PubMed] [Google Scholar]
  19. Like A. A., Rossini A. A., Guberski D. L., Appel M. C., Williams R. M. Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science. 1979 Dec 21;206(4425):1421–1423. doi: 10.1126/science.388619. [DOI] [PubMed] [Google Scholar]
  20. Like A. A., Weringer E. J., Holdash A., McGill P., Atkinson D., Rossini A. A. Adoptive transfer of autoimmune diabetes mellitus in biobreeding/Worcester (BB/W) inbred and hybrid rats. J Immunol. 1985 Mar;134(3):1583–1587. [PubMed] [Google Scholar]
  21. Logothetopoulos J., Valiquette N., Madura E., Cvet D. The onset and progression of pancreatic insulitis in the overt, spontaneously diabetic, young adult BB rat studied by pancreatic biopsy. Diabetes. 1984 Jan;33(1):33–36. doi: 10.2337/diab.33.1.33. [DOI] [PubMed] [Google Scholar]
  22. Naji A., Silvers W. K., Bellgrau D., Barker C. F. Spontaneous diabetes in rats: destruction of islets is prevented by immunological tolerance. Science. 1981 Sep 18;213(4514):1390–1392. doi: 10.1126/science.6791286. [DOI] [PubMed] [Google Scholar]
  23. Naji A., Silvers W. K., Kimura H., Bellgrau D., Markmann J. F., Barker C. F. Analytical and functional studies on the T cells of untreated and immunologically tolerant diabetes-prone BB rats. J Immunol. 1983 May;130(5):2168–2172. [PubMed] [Google Scholar]
  24. Nakhooda A. F., Like A. A., Chappel C. I., Murray F. T., Marliss E. B. The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes. 1977 Feb;26(2):100–112. doi: 10.2337/diab.26.2.100. [DOI] [PubMed] [Google Scholar]
  25. Poussier P., Nakhooda A. F., Falk J. A., Lee C., Marliss E. B. Lymphopenia and abnormal lymphocyte subsets in the "BB" rat: relationship to the diabetic syndrome. Endocrinology. 1982 May;110(5):1825–1827. doi: 10.1210/endo-110-5-1825. [DOI] [PubMed] [Google Scholar]
  26. Reynolds C. W., Timonen T., Herberman R. B. Natural killer (NK) cell activity in the rat. I. Isolation and characterization of the effector cells. J Immunol. 1981 Jul;127(1):282–287. [PubMed] [Google Scholar]
  27. Robinson A. P., Puklavec M., Mason D. W. MRC OX-52: a rat T-cell antigen. Immunology. 1986 Apr;57(4):527–531. [PMC free article] [PubMed] [Google Scholar]
  28. Rossini A. A., Mordes J. P., Pelletier A. M., Like A. A. Transfusions of whole blood prevent spontaneous diabetes mellitus in the BB/W rat. Science. 1983 Feb 25;219(4587):975–977. doi: 10.1126/science.6823559. [DOI] [PubMed] [Google Scholar]
  29. Rossini A. A., Slavin S., Woda B. A., Geisberg M., Like A. A., Mordes J. P. Total lymphoid irradiation prevents diabetes mellitus in the Bio-Breeding/Worcester (BB/W) rat. Diabetes. 1984 Jun;33(6):543–547. doi: 10.2337/diab.33.6.543. [DOI] [PubMed] [Google Scholar]
  30. Seemayer T. A., Tannenbaum G. S., Goldman H., Colle E. Dynamic time course studies of the spontaneously diabetic BB Wistar rat. III. Light-microscopic and ultrastructural observations of pancreatic islets of Langerhans. Am J Pathol. 1982 Feb;106(2):237–249. [PMC free article] [PubMed] [Google Scholar]
  31. Sternthal E., Like A. A., Sarantis K., Braverman L. E. Lymphocytic thyroiditis and diabetes in the BB/W rat. A new model of autoimmune endocrinopathy. Diabetes. 1981 Dec;30(12):1058–1061. doi: 10.2337/diab.30.12.1058. [DOI] [PubMed] [Google Scholar]
  32. Waldor M. K., Sriram S., Hardy R., Herzenberg L. A., Herzenberg L. A., Lanier L., Lim M., Steinman L. Reversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker. Science. 1985 Jan 25;227(4685):415–417. doi: 10.1126/science.3155574. [DOI] [PubMed] [Google Scholar]
  33. Woda B. A., Like A. A., Padden C., McFadden M. L. Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. J Immunol. 1986 Feb 1;136(3):856–859. [PubMed] [Google Scholar]
  34. Woda B. A., McFadden M. L., Welsh R. M., Bain K. M. Separation and isolation of rat natural killer (NK) cells from T cells with monoclonal antibodies. J Immunol. 1984 May;132(5):2183–2184. [PubMed] [Google Scholar]
  35. Wofsy D., Seaman W. E. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med. 1985 Feb 1;161(2):378–391. doi: 10.1084/jem.161.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]

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