INTERFERON-γ (IFN-γ) is produced during the response to infection and participates in immunostimulatory events. We have previously reported the induction of diabetes in transgenic mice (ins-IFN-γ) in which the expression of the lymphokine IFN-γ is directed by the insulin promoter1. This diabetes is a result of the progressive destruction of pancreatic islets that occurs with the influx of inflammatory cells. Here we demonstrate that this islet cell loss is mediated by lymphocytes, that engrafted histocompat-ible islets are destroyed, and that lymphocytes from the transgenic mice are cytotoxic to normal islets in vitro. These results indicate that the pancreatic expression of IFN-γ can result in a loss of tolerance to normal islets, consistent with its role as an inducer of costimulatory activity2,3, which is essential for lymphocyte activation during an immune response.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Sarvetnick, N., Liggitt, D., Pitts, S. L., Hansen, S. E. & Stewart, T. A. Cell 52, 773–782 (1988).
Hawrylowicz, C. M. & Unanue, E. R. J. Immun. 141, 4083–4088 (1988).
Weaver, C. T., Hawrylowicz, C. M. & Unanue, E. R. Proc. natn. Acad. Sci. U.S.A. 85, 8181–8185 (1988).
Bosma, C. G., Custer, R. P. & Bosma, M. J. Nature 301, 527 (1983).
Duijvestijn, A. M., Schreiber, A. B. & Butcher, E. C. Proc. natn. Acad. Sci. U.S.A. 83, 9114–9118 (1986).
Brown, J., Molnar, I. G., Clark, W. & Mullen, Y. Science 184, 1377–1379 (1974).
Kemp, C. V., Knight, M. G., Scharp, D. W., Lacy, P. E. & Ballinger, W. F. Nature 244, 447 (1973).
Campbell, I. L., Iscaro, A. & Harrison, L. C. J. Immun. 141, 2325 (1988).
Harrison, L. C., Campbell, I. C., Allison, J. & Miller, J. F. A. P. Diabetes 38, 815–818 (1989).
Mitchison, N. A. Immunology 15, 509–530; 531–547 (1968).
Hooper, D. C., Young, J. L., Elson, C. J. & Taylor, R. B. Cell. Immun. 106, 53–61 (1987).
Hooper, D. C. & Taylor, R. B. Eur. J. Immun. 17, 797 (1987).
Rammensee, H. G., Kroschewski, R. & Frangoulis, B. Nature 339, 541–544 (1989).
Qin, S., Cubbold, S., Benjamin, R. & Waldmann, H. J. exp. Med. 169, 779–794 (1989).
Markmann, J. et al. Nature 336, 476–479 (1988).
Burkly, L. C., Lo, D., kanagawa, O., Brinster, R. L. & Flavell, R. A. Nature 342, 564–566 (1989).
Lo, D., Burkly, L. C., Flavell, R. A., Palmiter, R. D. & Brinster, R. L. J. exp. Med. 170, 87–104 (1989).
Bohme, J. et al. Science 211, 1179–1183 (1989).
Murphy, K. M., Weaver, C. T., Elish, M., Allen, P. M. & Loh, D. Y. Proc. natn. Acad. Sci. U.S.A. 86, 10034–10038 (1989).
Rights and permissions
About this article
Cite this article
Sarvetnick, N., Shizuru, J., Liggitt, D. et al. Loss of pancreatic islet tolerance induced by β-cell expression of interferon-γ. Nature 346, 844–847 (1990). https://doi.org/10.1038/346844a0
This article is cited by
The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway
Surgery Today (2019)
Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review
Applied Biological Chemistry (2017)
Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes
Nature Reviews Immunology (2004)
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.