Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice

Abstract

KNOWING the autoantigen target(s) in an organ-specific autoimmune disease is essential to understanding its pathogenesis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by lymphocytic infiltration of the islets of Langerhans (insulitis) and destruction of insulin-secreting pancreatic β-cells1. Several β-cell proteins have been identified as autoantigens, but their importance in the diabetogenic process is not known2. The non-obese diabetic (NOD) mouse is a murine model for spontaneous IDDM3. Here we determine the temporal sequence of T-cell and antibody responses in NOD mice to a panel of five murine β-cell antigens and find that antibody and T-cell responses specific for the two isoforms of glutamic acid decarboxylase (GAD) are first detected in 4-week-old NOD mice. This GAD-specific reactivity coincides with the earliest detectable response to an islet extract, and with the onset of insulitis. Furthermore, NOD mice receiving intrathymic injections of GAD65 exhibit markedly reduced T-cell proliferative responses to GAD and to the rest of the panel, in addition to remaining free of diabetes. These results indicate that the spontaneous response to β-cell antigens arises very early in life and that the anti-GAD immune response has a critical role in the disease process during this period.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Eisenbarth, G. S. New Engl. J. Med. 314, 1360–1368 (1986).

    Article  CAS  Google Scholar 

  2. Harrison, L. C. Immun. Today 13, 348–352 (1992).

    Article  CAS  Google Scholar 

  3. Makino, S. et al. Expl Anim. 29, 1 (1980).

    Article  CAS  Google Scholar 

  4. Baekkeskov, S. et al. Nature 298, 167–169 (1982).

    Article  ADS  CAS  Google Scholar 

  5. Baekkeskov, S. et al. Nature 347, 151–166 (1990).

    Article  ADS  CAS  Google Scholar 

  6. Honeyman, M. C., Cram, D. S. & Harrison, L. C. J. exp. Med. 177, 535–540 (1993).

    Article  CAS  Google Scholar 

  7. Boitard, C. et al. Proc. natn. Acad. Sci. U.S.A. 89, 172–176 (1992).

    Article  ADS  CAS  Google Scholar 

  8. Castano, L., Russo, E., Zhou, L., Lipes, M. A. & Eisenbarth, G. S. J. clin. Endocrin. Metab. 73, 1197–1201 (1991).

    Article  CAS  Google Scholar 

  9. Elias, D., Markovits, D., Reshef, T., van der Zee, R. & Cohen, I. R. Proc. natn. Acad. Sci. U.S.A. 87, 1576–80 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Shizuru, J., Taylor-Edwards, C., Banks, B. A., Gregory, A. K. & Fathman, C. G. Science 240, 659–662 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Miller, B. J., Appel, M. C., O'Neil, J. J. & Wicker, L. S. J. Immun. 140, 52–58 (1988).

    CAS  PubMed  Google Scholar 

  12. Hayward, A. & Schreiber, M. J. Immun. 143, 1555–1559 (1989).

    CAS  PubMed  Google Scholar 

  13. Reich, E. P., Sherwin, R. S., Kanagawa, O. & Janeway, C. A. Nature 341, 326–328 (1989).

    Article  ADS  CAS  Google Scholar 

  14. Leffert, J. D., Newgard, C. B., Okamoto, H., Miburn, J. L. & Luskey, K. L. Proc. natn. Acad. Sci. U.S.A. 86, 3127–3130 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Prochazka, M., Serreze, D. V., Frankel, W. N. & Leiter, E. H. Diabetes 41, 98–106 (1992).

    Article  CAS  Google Scholar 

  16. Gerling, I. C. et al. Diabetes 41, 1672–1676 (1992).

    Article  CAS  Google Scholar 

  17. Coffman, R. L. et al. Immun. Rev. 102, 5–28 (1988).

    Article  CAS  Google Scholar 

  18. Atkinson, M. A. et al. Lancet 339, 458–459 (1992).

    Article  CAS  Google Scholar 

  19. O'Reilly, D. R., Miller, L. K. & Luckow, V. A. Baculovirus Expression Vectors: A Laboratory Manual (Freeman, New York, 1992).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tisch, R., Yang, XD., Singer, S. et al. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366, 72–75 (1993). https://doi.org/10.1038/366072a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/366072a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing