Advertisement

Autoantigens Produced in Plants for Oral Tolerance Therapy of Autoimmune Diseases

  • Shengwu Ma
  • A. M. Jevnikar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 464)

Abstract

Oral administration of protein antigens can induce antigen-specific immune hy-poresponsiveness and may be useful in treating autoimmune diseases or preventing transplant rejection. However, the therapeutic value of oral tolerance may be limited when candidate autoantigens cannot be produced by conventional system in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can produce hugh quantities of functional mammalian proteins at extremely competitive cost. Furthermore, transgenic food plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Here we show that the diabetes-associated autoantigen glutamic acid decarboxylase (GAD) is efficiently expressed in both tobacco and potato plants, and that mice, when fed with fresh transgenic potato tubers, are fully protected from diabetes.

Keywords

Transgenic Plant Major Histocompatibility Complex Major Histocompatibility Complex Class Myelin Basic Protein Glutamic Acid Decarboxylase 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Atkinson, M. A.; Maclaren, N. K. Autoantibodies in nonobese diabetic mice immunoprecipitate 64,000-Mr islet antigen. Diabetes 1988, 37, 1587–1590.PubMedCrossRefGoogle Scholar
  2. Atkinson, M. A.; Maclaren, N.K. The pathogenesis o/insulin-dependent diabetes millitus. New. Eng. J. Med. 1994, 331, 142–1436Google Scholar
  3. Atkinson, M. A.; Bowmam, M. A.; Campbell, L.; Darrow, B. L.; Kaufman, D. L.; Maclaren, N. K. Cellular immunity to a determinant common to glutamate decarboxylase and Coxsackie virus in insulin-dependent diabetes. J. Clin. Invest. 1994, 94, 2125–2129PubMedCrossRefGoogle Scholar
  4. Bosi, E.; Botazzo, G.F. Autoimmunity in insulin-dependent diabetes mellitus. 1995. Clin. Immunother. 1995, 3, 125–135CrossRefGoogle Scholar
  5. Bu, D. F.; Erlander, M.G. Two human glutamate decarboxylases 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Pro. Natl. Acad. Sci. USA. 1992, 89, 2115–2119.CrossRefGoogle Scholar
  6. Burstein, H. J.; Abbas, A. K. In vivo role of interleukin 4 in T cell tolerance induced by aqueous protein antigen. J. Exp. Med. 1993, 177, 457–463.PubMedCrossRefGoogle Scholar
  7. Castano, L.; Eisenbarth, G. S. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu. Rev. Immunol. 1990, 8, 647–679.PubMedCrossRefGoogle Scholar
  8. Challacombe, S. J,; Tomasi, T. J. Systemic tolerance and secretory immunity after oral immunization. J. Exp. Med. 1980, 152, 1459–1472PubMedCrossRefGoogle Scholar
  9. Chase, M. Inhibition of experimental drug allergy by prior feeding of the sensitizing agent. Proc. Soc. Exp. Bio. Med. 1946, 61,257–259.Google Scholar
  10. Dalsgaard, K. Uttenthal, A.; Jones, T. D.; Xu, F.; Merryweather, A.; Hamilton, W. D. O.; Langeveld, J. P. M; Boshuizen, R. S.; Kamstrup, S.; Lomonossoff, G. P.; Porta, C.; Vela, C.; Casal, J.-L; Meloen, R. H.; Rodg-ers, P. B. Plant-derived vaccine protects target animals against a viral disease. Nature Biotechnol. 1997, 15, 248–252.CrossRefGoogle Scholar
  11. Ellitt, J. F.; Qin, H.Y.; Bhatti, S.; Smith, D. K.; Singh, R. K.; Fraga, E.; Dillon, T.; Lauzon, J.; Singh, B. Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice. Diabetes 1994, 43, 1494–1499CrossRefGoogle Scholar
  12. Finkelman, F.D.; Holmes, J.; Katona, I.M.; Urban, Jr.; Beckmann, M.P.; Park, L.S.; Schooley, K.A.; Coffman, R.L.; Mosmann, T.R.; Paul, W.E. Lymphokine control of in vivo immunoglobulin isotype selection. Annu. Rev. Immunol. 1990, 8, 303–333.PubMedCrossRefGoogle Scholar
  13. Fukaura, H.; Kent, S. C.; Pietrusewicz, M. J.; Khoury, S. J.; Weiner, H. L.; Hafler, D. A. Induction of circulating myelin basic protein and proteolipid protein specific TGF-β-1 secreting T cells by oral administration of myelin in multiple sclerosis patients. J. Clin. Invest. 1996, 98, 70–77.PubMedCrossRefGoogle Scholar
  14. Ganz, P. R.; Dudani, A. K.; Tackaberry, E. S.; Sardana, R.; Sauder, C; Cheng, X. Y.; Altosaar, I. Expression of human blood proteins in transgenic plants: the cytokine GM-CSF as a model protein. In transgenic plants: A production system for industrial and pharmaceutical proteins. Owen, M. R. L., Pen, J., eds.; John Wiley & Sons, New York, 1996, pp.281–297.Google Scholar
  15. Germain, R. N.; Margulies, D. M. The biochemistry and cell biology of antigen processing and presentation. Annu. Rev. Immunol 1993,11, 403–450.PubMedCrossRefGoogle Scholar
  16. Haq, T.A., Mason, H.S., Clements, J.D. and Arntzen, C.J. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 1995, 268, 714–716PubMedCrossRefGoogle Scholar
  17. Kaufman, D. L.; Clare-Salzler, M.; Tian, J.; Forsthuber, T.; Ting, G. S.; Robinson, P.; Atkinson, M. A.; Sercarz, E. E.; Tobin, A. J.; Lehmann, P. V. Spontaneous loss of T cell tolerance to glutamic acid decarboxylase in murine insulin dependent diabetes. Nature 1993, 366, 69–72.PubMedCrossRefGoogle Scholar
  18. Klein, J. In Natural history of the major hiscocompatibility complex. John Wiley and Sons, New York, 1986.Google Scholar
  19. Krensky, A. M.; Crabtree, W. G.; Davis, M. M.; Parham, P. T-lymphocyte-antigen interactions in transplant rejection. New Engl. J. Med. 1990, 322, 510–517.PubMedCrossRefGoogle Scholar
  20. Liblau, R. S.; Singer, S. M.; McDevitt, H. O. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today 1995, 16, 34–38.PubMedCrossRefGoogle Scholar
  21. Ma, S. W.; Zhao, D. L.; Yin, Z. Q.; Mukherjee, R.; Singh, B.; Qin, H.Y.; Stiller, CR.; Jevnikar, A.M. Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance. Nature Medicine 1997, 3, 793–796PubMedCrossRefGoogle Scholar
  22. Maclaren, N. K.; Atkinson, M. A. Insulin-dependent diabetes mellitus: the hypothesis of molecular mimicry between islet cell antigens and microorganisms. Mol Medi. Today 1997, 2, 76–83.CrossRefGoogle Scholar
  23. McGarvey, P. B.; Hammond, J.; Dienelt, M. M.; Hooper, D. C; Fu, Z. F.; Dietzschold, B.; Koprowski, H.; Michaels, F. H. Expression of the rabies virus glycoprotein in transgenic tomatoes. Bio/Technology 1995, 13, 1484–1487.PubMedCrossRefGoogle Scholar
  24. Makino, S.; Hunimoto, K.; Muraoka, Y.; Katagiri, K. Effects of castration on the appearance of diabetes in NOD mice. Exp. Anim. 1981, 3, 137–140.Google Scholar
  25. Mason, H. S.; Ball, J. M.; Shi, J.-J.; Jiang, X.; Estes, M. K.; Arntzen, C. J. Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral Immunogenicity in mice. Proc. Nati. Acad. Sei. USA 1996, 93, 5335–5340.CrossRefGoogle Scholar
  26. Mossmann, T.R.; Coffman, R.L. Thl and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol 1989, 7, 145CrossRefGoogle Scholar
  27. Mowat, A.M. The regulation of immune responses to dietary protein antigens. Immunol Today 1987, 8, 93–98.CrossRefGoogle Scholar
  28. Nussenblatt, R. B.; Gery, I.; Weiner, H. L.; Ferris, F. L.; Shiloach, J.; Remaley, N.; Perry, C; Caspi, R. R.; Hafler, D. A.; Foster, C. S.; Whitcup, S. M. Traetment of Uveitis by oral administration of retinal antigens: results of a phase I/II randomized masked trial. Am. J. Ophthalmol 1997,123, 583–592.PubMedGoogle Scholar
  29. Porcelli, S. Molecular mimicry and the generation of autoimmune diseases. Rheumatol. Rev. 1993, 2, 41–50.Google Scholar
  30. Powrie, F.; Coffman, R. L. Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunol Today 1993, 14, 270–274.PubMedCrossRefGoogle Scholar
  31. Rabinovich, A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation. Diabetes 1994, 43, 613–621.CrossRefGoogle Scholar
  32. Sayegh, M. H.; Khoury, S. J.; Hancock, W. W.; Weiner, H. L.; Carpenter, C. B. Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat. Proc. Natl. Acad. Sci. USA. 1992, 89,772–7766.CrossRefGoogle Scholar
  33. Schwartz, R. H. T lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu. Rev. Immunol. 1985, 3, 237–261.PubMedCrossRefGoogle Scholar
  34. Scott, M.; Schatz, D.; Atkinson, M.; Krischer, J.; Mehta, H.; Vold, B.; Maclaren, N. GAD65 autoantibodies increase the predictability but not the sensitivity of islet cell and insulin antoantibodies for developing insulin dependent diabetes mellitus patients. J. Autoimmun. 1994, 7, 865–872.CrossRefGoogle Scholar
  35. Szopa, T. M.; Tichener, P. A.; Portwood, N. D.; Taylor, K. W. Diabetes mellitus due to viruses. Some recent developments. Diabetologia 1993, 36, 687–695.PubMedCrossRefGoogle Scholar
  36. Tian, J.; Atkinson, M. A.; Clare-Salzler, M.; Herschenfeld, A.; Forsthuber, T.; Lehmann, P.; Kaufman, D, L. Nasal administration of glutamic acid decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. J. Exp. Med. 1996,183,1561–1567.PubMedCrossRefGoogle Scholar
  37. Tisch, R.; Yang, X. D.; Singer, S. M.; Liblau, R. S.; Fugger, L.; McDevitt, H. O. Immune response to glutamic acid decarboxylase correlates with insulitis in nonobese diabetic mice. Nature 1993, 366,72–75.PubMedCrossRefGoogle Scholar
  38. Titus, R. G.; Chiller, J. M. Oral induced tolerance. Definition at the cellular level. Int. Arch. Allergy App. Immunol. 1982, 65,321–326.Google Scholar
  39. Weiner, H. L. Oral tolerance for the treatment of autoimmune diseases. Annu. Rev. Med. 1997, 48, 341–351.PubMedCrossRefGoogle Scholar
  40. Weiner, H.L.; Friedman, A.; Miller, A.; Khoury, S.J.; Al-Sabbagh, A.; Santos, L.; Sayegh, M.; Nussenblatt. R.; Trentham, D.E.; Hafler, D.A. Oral tolerance: Immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu. Rev. Immunol 1994, 12,809–837.PubMedCrossRefGoogle Scholar
  41. Wells, H. Studies on the chemistry of anaphylaxis. III. Experiments with isolated proteins, especially those of hen’s egg. J. Infect. Dis. 1911, 9, 147–151.CrossRefGoogle Scholar
  42. Wicker, L. S.; Miller, B. J.; Mullen, Y. Transfer of autoimmune diabetes mellitus with splenocytes from non-obese diabetic (NOD) mice. Diabetes 1986, 35, 855–860.PubMedCrossRefGoogle Scholar
  43. Wicker, L. S., Todd, J. A.; Peterson, L. B. Genetic control of autoimmune diabetes in the NOD mouse. Annu. Rev. Immunol 1995, 13, 179–200.PubMedCrossRefGoogle Scholar
  44. Wucherpfening, K. W.; Strominger, J. L. Molecular mimicry in T-cell mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995, 80, 695–705.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Shengwu Ma
    • 1
  • A. M. Jevnikar
    • 1
  1. 1.John P. Robarts Research Institute and Siebens-Drake Research InstituteUniversity of Western Ontario; and London Health Sciences CentreLondonCanada

Personalised recommendations