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Transgenic mice carrying the rearranged T cell receptor of a diabetogenic T cell clone

  • Jonathan D. Katz
  • Bo Wang
  • Christophe Benoist
  • Diane Mathis
Conference paper
Part of the NATO ASI Series book series (volume 80)

Abstract

Insulin-dependent diabetes mellitus (IDDM) is a progressive autoimmune disease that results in destruction of the insulin-producing beta cells in the pancreatic islets of langerhans (reviewed in Castano and Eisenbarth, 1990). The genetic and environmental factors which provoke this disease in humans remain largely unknown. Fortunately, the nonobese diabetic (NOD) mouse develops a spontaneous diabetes remarkably similar to that in humans and has thus greatly facilitated its study (Makino et al, 1980). The disease of NOD mice parallels that of the human in that it first develops as an occult infiltration of lymphocytes into the islets, a process termed insulitis, followed by the destruction of the overwhelming majority of the beta cells, thereby, percipitating an overt diabetes. Autoimmune diabetes in NOD mice is under polygenic control, with the most important single contributor being the major histocompatibility complex (MHC) - \(H - {2^{{g^7}}}\).

Keywords

Transgenic Mouse Major Histocompatibility Complex Class Islet Cell Overt Diabetes Nonobese Diabetic Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Bendelac, A., Carnaud, C., Boitard, C., and Bach, J-F. (1987). Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. J. Exp. Med. 166, 823–832.PubMedCrossRefGoogle Scholar
  2. Blackman, M.A., Gerhard-Burgert, H., Woodland, D.L., Palmer, E., Kappler, J.W., and Marrack, P. (1990). A role for clonal inactivation in T cell tolerance to Mls-la. Nature 345, 540–542.PubMedCrossRefGoogle Scholar
  3. Blüthmann, H., Kisielow, P., Uematsu, Y., Malissen, M., Krimpenfort, P., Berns, A. (1988). T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous a- and ß-genes. Nature 334, 156–159.PubMedCrossRefGoogle Scholar
  4. Böhme, J., Schuhbaur, B., Kanagawa, O., Benoist, C., Mathis, D. (1990). MHC– linked protection from diabetes dissociated from clonal deletion of T cells. Science 249, 293–295PubMedCrossRefGoogle Scholar
  5. Bradley, B.J., Haskins, K., La Rosa, F.G., Lafferty, K.J. (1992). CD8 T cells are not required for islet destruction induced by a CD4+ islet-specific T-cell clone. Diabetes 41, 1603–1608.PubMedCrossRefGoogle Scholar
  6. Carlow, D.A., Teh, S-J., and Teh, H-S. (1992). Altered thymocyte development resulting from expressing a deleting ligand on selecting thymic epithelium. J. Immunol. 148, 2988–2995.PubMedGoogle Scholar
  7. Castano, L., and Eisenbarth, G.S. (1990). Type-I diabetes: A chronic autoimmune disease of human, mouse and rat. Ann. Rev. Immunol. 8, 647–679.Google Scholar
  8. Dardenne, M., Lepault, F., Bendelac, A., and Bach, J–F. (1989). Acceleration of the onset of diabetes in NOD mice by thymectomy at weaning. Eur. J. Immunol. 19, 889–895.Google Scholar
  9. Deng, H., Apple, R., Clare-Salzler, M., Trembleau, S., Adorini, L., Sercarz, E. (1993). Determinant capture as a possible mechanism of protection afforded by MHC class II molecules in insulin-dependent diabetes mellitus, in press J. Exp. Med.Google Scholar
  10. Garchon, H-J., (1992). Non-MHC-linked genes in autoimmune diseases. Curr. Opin. in Immunol. 4, 716–722.CrossRefGoogle Scholar
  11. Harada, M., and Makino, S. (1986). Suppression of overt diabetes in NOD mice by anti-thymocyte serum or anti-Thy 1. 2 antibody. Exp. Anim. 35, 501–506.Google Scholar
  12. Haskins, K., Portas, M., Bradley, B., Wegmann, D., Lafferty, K.J. (1988). T-lymphocyte clone specific for pancreatic islet antigen. Diabetes 37, 1444–1448.PubMedCrossRefGoogle Scholar
  13. Haskins, K., Portas, M., Bergman, B., Lafferty, K., Bradley B. (1989). Pancreatic islet-specific T-cell clones from nonobese diabetic mice. Proc. Natl. Acad. Sei. USA 86, 8000–8004.Google Scholar
  14. Haskins, K., and McDuffie, M. (1990). Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T-cell clone. Science 249, 1433–1436.PubMedCrossRefGoogle Scholar
  15. Schonrich, G., Momburg, F., Hammerling, G.J., and Arnold, B. (1992a). Anergy induced by thymic medullary epithelium. Eur. J. Immunol. 22, 1687–1691.Google Scholar
  16. Schonrich, G., Momburg, F., Malissen M., Schmitt-Verhulst, A-M., Malissen, B., Hammerling, G.J., and Arnold, B. (1992b). Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self antigen. Int. Immunol. 4,581– 590.Google Scholar
  17. Sempe, P., BMossa, P., Richard, M-F., Villa, M-C., Bach, J-F., and Boitard, C. (1991). Anti-a/b T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic NOD mice. Eur. J. Immunol. 21, 1663–1169.Google Scholar
  18. Sha, W.C. Nelson, C.A., Newberry, R.D., Kranz, D.M., Russell, J.H., and Loh, D.Y. (1988). Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature 336, 73–76.Google Scholar
  19. Shizuru, J.A., Taylor-Edwards, C., Banks, B.A., Gregory, A.K., Fathman, C.G. (1988). Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes. Science 240, 659–662.PubMedCrossRefGoogle Scholar
  20. Signorelli, K., Benoist, C., and Mathis, D. (1992). Why is clonal deletion of neonatal thymocytes defective ? Eur. J. Immunol. 22, 2487–2493.PubMedCrossRefGoogle Scholar
  21. Thivolet, C., Bendelac, A., Bedossa, P., Bach, J-F., and Carnaud, C. (1991). CD8+ T cell homing to the pancreas in the nonobese diabetic mouse is CD4+ T cell-dependent. J. Immunol. 146, 85–88.PubMedGoogle Scholar
  22. Uehira, M., Uno, M., Kiirner, T., Kikutani, H., Mori, K-I., Inomoto, T., Uede, T., Miyazaki, J-I., Nishimoto, H., Kishimoto, T., and Yamamura, K-I. (1989). Development of autoimmune insulitis is prevented in Ead but not in Apk NOD transgenic mice. Int. Immunol. 1, 210–213.Google Scholar
  23. Uematsu, Y., Ryser, S., Dembic, Z., Borgulya, P., Krimpenfort, P., Berns, A., von Boehmer, H., and Steinmetz, M. (1988). In transgenic mice the introduced functional T cell receptor p gene prevents expression of endogenous p genes. Cell 52, 831–841.PubMedCrossRefGoogle Scholar
  24. Uno, M., Miyazaki, T., Uehira, M., Nishimoto, H., Kimoto, M., Miyazaki, J-I., and Yamamura, K-I. (1991). Complete prevention of diabetes in transgenic NOD mice expressing I-E molecules. Immunol. Lett. 31, 47–52.Google Scholar
  25. Yagi, H., Matsumoto, M., Kunimoto, K., Kawaguchi, J., Makino, S., and Harada, M. (1992). Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes of NOD mice using transfer to NOD athymic nude mice. Eur. J. Immunol. 22, 2387–2393.Google Scholar
  26. Mori, Y., Suko; M., Okudaira, H., Matsuba, I., Tsuruoka, A., Sasaki, A., Yokoyama, H., Tanase, T., Shida, T., Nishimura, M., Terada, E., and Ikeda, Y. (1986). Preventive effects of cyclosporin on diabetes in NOD mice. Diabetologia 29, 244–248.Google Scholar
  27. Nagata, M., Yokono, K., Hayakawa, M., Kawase, Y., Hatamori, N., Ogawa, W., Yonezama, K., Shil, K., and Baba, S. (1989). Destruction of pancreatic islet cells by cytotoxic T lymphocytes in nonobese diabetic mice. J. Immunol. 143, 1155–1162.PubMedGoogle Scholar
  28. Nagata, M., and Yoon J-W. (1992). Studies on Autoimmunity for T-cell-Mediated ß-cell destruction. Diabetes 41, 998–1008.PubMedCrossRefGoogle Scholar
  29. Nakano, N., Kikutani, H., Nishimoto, H., and Kishimoto, T. (1991). T cell receptor V gene usage of islet ß cell-reactive T cells is not restricted in non–obese diabetic mice. J. Exp. Med. 173, 1091–1097.Google Scholar
  30. Nishimoto, H., Kikutani, H., Yamamura, K-I., and Kishimoto, T. (1989). Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice. Nature 328, 432–434.CrossRefGoogle Scholar
  31. Ogawa, M., Maruyama, T., Hasegawa, T., Kanaya, T., Kobayashi, F., Tochino, Y., Uda, H. (1985). The inhibitory effect of neonatal thymectomy on the incidence of insulitis in non-obese diabetes (NOD) mice. Biomed. Res. 6, 103–105.Google Scholar
  32. Ohashi, P.S., Pircher, H., Mak, T.W., Burki, K., Zinkernagel, R.M., and Hengatner, H. (1989). Ontogeny and selection of the T cell repertoire in transgenic mice. Semin. Immunol. 1, 95–104.Google Scholar
  33. Ohashi, P.S., Oehen, S., Buerki, K., Pircher, H., Ohashi, C.T., Odermatt, B., Malissen, B., Zinkernagel, R.M., and Hengartner, H. (1991). Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65, 305–317.PubMedCrossRefGoogle Scholar
  34. Pankewycz, O., Strom, T.R., and Rubin-Kelley, V.E.R. (1991). Islet-infiltrating T cell clones from non-obese diabetic mice that promote or prevent accelerated onset diabetes. Eur. J. Immunol. 21, 873–879.Google Scholar
  35. Reich, E-P., Sherwin, R.S., Kanagawa, O., and Janeway, Jr, C.A. (1989). An explanation for the protective effect of the MHC class II I-E molecule in murine diabetes. Nature 341, 326–328.PubMedCrossRefGoogle Scholar
  36. Rocha, B., and von Boehmer, H. (1991). Peripheral selection of the T cell repertoire. Science 251, 1225–1228.PubMedCrossRefGoogle Scholar
  37. Schönrich, G., Kalinke, U., Momburg, F., Malissen, M., Schmitt-Verhulst, A-M., Malissen, B., Hämmer ling, G.J., and Arnold, B. (1991). Down-regulation of T cell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction. Cell 65, 293–304.PubMedCrossRefGoogle Scholar
  38. Schonrich, G., Momburg, F., Hammerling, G.J., and Arnold, B. (1992a). Anergy induced by thymic medullary epithelium. Eur. J. Immunol. 22, 1687–1691.Google Scholar
  39. Schonrich, G;, Momburg, F., Malissen M., Schmitt-Verhulst, A-M., Malissen, B., Hammerling, G.J., and Arnold, B. (1992b). Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self antigen. Internat. Immunol. 4, 581–590.Google Scholar
  40. Semp£, P., Bedossa, P., Richard, M-F., Villa, M-C., Bach, J-F., and Boitard, C. (1991). Anti-a/b T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic NOD mice. Eur. J. Immunol. 21, 1663–1169.Google Scholar
  41. Sha, W.C. Nelson, C.A., Newberry, R.D., Kranz, D.M., Russell, J.H., and Loh, D.Y. (1988). Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature 336, 73–76.PubMedCrossRefGoogle Scholar
  42. Shizuru, J.A., Taylor-Edwards, C., Banks, B.A., Gregory, A.K., Fathman, C.G. (1988). Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T–helper lymphocytes. Science 240, 659–662.PubMedCrossRefGoogle Scholar
  43. Signorelli, K., Benoist, €., and Mathis, D. (1992). Why is clonal deletion of neonatal thymocytes defective ? Eur. J. Immunol. 22, 2487–2493.Google Scholar
  44. Thivolet, C., Bendelac, A., Bedossa, P., Bach, J-F., and Carnaud, C. (1991). CD8+ T cell homing to the pancreas in the nonobese diabetic mouse is CD4+ T cell-dependent. J. Immunol. 146, 85–88.PubMedGoogle Scholar
  45. Uehira, M., Uno, M., Kiirner, T., Kikutani, H., Mori, K-I., Inomoto, T., Uede, T., Miyazaki, J-I., Nishimoto, H., Kishimoto, T., and Yamamura, K–I. (1989). Development of autoimmune insulitis is prevented in Ead but not in Apk NOD transgenic mice. Internat. Immunol. 1, 210–213.Google Scholar
  46. Uematsu, Y., Ryser, S., Dembic, Z., Borgulya, P., Krimpenfort, P., Berns, A., von Boehmer, H., and Steinmetz, M. (1988). In transgenic mice the introduced functional T cell receptor p gene prevents expression of endogenous p genes. Cell 52, 831–841.PubMedCrossRefGoogle Scholar
  47. Uno, M., Miyazaki, T., Uehira, M., Nishimoto, H., Kimoto, M., Miyazaki, J-I., and Yamamura, K-I. (1991). Complete prevention of diabetes in transgenic NOD mice expressing I–E molecules. Immunol. Lett. 31, 47–52.Google Scholar
  48. Yagi, H., Matsumoto, M., Kunimoto, K., Kawaguchi, J., Makino, S., and Harada, M. (1992). Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes of NOD mice using transfer to NOD athymic nude mice. Eur. J. Immunol. 22, 2387–2393.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Jonathan D. Katz
    • 1
  • Bo Wang
    • 1
  • Christophe Benoist
    • 1
  • Diane Mathis
    • 1
  1. 1.Faculté de MédecineLaboratoire de Génétique Moléculaire des Eukaryotes du CNRS et Unité 184 - Biologie Moléculaire et Génie Génétique de l’INSERMStrasbourg CédéxFrance

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