Abstract
HLA class II molecules are surface glycoproteins which are essential in the initiation of immune responses. It has been postulated that induction of class II in epithelial cells such as endocrine cells, which are normally class II negative1, may result in autoimmunity2. In type I diabetes, islet beta cells, the target of the autoimmune process, selectively express class II antigens3,4. But in contrast to most other cell types5, islet beta cells are not stimulated to express class II by interferon-γ (IFN-γ)6,7 and thus the conditions under which this induction occurs have been particularly elusive. The cytotoxins tumour necrosis factor (TNF) and lymphotoxin (LT) synergize with IFN-γ in a number of activities8. We report here that IFN-γ in combination with either TNF or LT induces islet cell class II expression. This finding has important implications for the pathogenesis of type I diabetes and the understanding of the differential control of class II expression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Baekkeskov, S. et al. Proc. natn. Acad. Sci. U.S.A. 78, 6456–6460 (1981).
Bottazzo, G. F., Pujol-Borrell, R., Hanafusa, T. & Feldmann, M. Lancet ii, 1115–1119 (1983).
Bottazzo, G. F. et al. New Engl. J. Med. 313, 353–360 (1985).
Foulis, A. K. & Farquharson, M. A. Diabetes 35, 1215–1224 (1986).
Todd, I. et al. Clin. exp. Immun. 61, 265–273 (1985).
Pujol-Borrell, R. et al. Clin. exp. Immun. 65, 128–139 (1986).
Campbell, I. L. et al. J. clin. Endocr. Metab. 62, 1101–1109 (1986).
Wong, G. W. & Goeddel, D. V. Nature 323, 819–822 (1986).
Pujol-Borrell, R., Hanafusa, T., Chiovato, L. & Bottazzo, G. F. Nature 303, 71–73 (1983).
Hanafusa, T. et al. Lancet ii, 1111–1115 (1983).
Londei, M., Lamb, J. R., Borrazzo, G. F. & Feldmann, M. Nature 312, 639–641 (1984).
Londei, M., Bottazzo, G. F. & Feldmann, M. Science 228, 85–89 (1985).
Pujol-Borrell, R. & Todd, I. Balliere's Clin. Immun. Allergy (in the press).
Beutler, B. & Cerami, A. Nature 320, 584–588 (1986).
Bendtzen, K. et al. Science 232, 1545–1547 (1986).
Walker, E. B. et al. J. exp. Med. 159, 1532–1547 (1984).
Gray, P. W. et al. Nature 312, 721–724 (1984).
Pennica, D. et al. Nature 312, 724–729 (1984).
Stone-Wolff, D. S. et al. J. exp. Med. 159, 828–843 (1984).
Lee, S. H. et al. J. Immun. 133, 1083–1086 (1984).
Shalaby, M. R. et al. J. Immun. 135, 2069–2073 (1985).
Philip, R. & Epstein, L. B. Nature 323, 86–89 (1986).
Pober, J. S. J. Immun. 137, 1893–1896 (1986).
Collins, T. et al. Proc. natn. Acad. Sci. U.S.A. 83, 446–450 (1986).
Todd, I., McNally, J. M., Hammond, L. J. & Pujol-Borrell, R. in Frontiers in Thyroidology (eds Gaitan, E. & Mederos-Neto, G.) 1551–1554 (Plenum, New York, in the press).
Acres, R. B., Lamb, J. R. & Feldmann, M. Immunology 54, 9–16 (1985).
Todd, I., Pujol-Borrell, R., Hammond, L. J., McNally, J. M., Feldmann, M. & Bottazzo, G. F. Clin. exp. Immun. (submitted).
Gray, D. W. R., McShane, P., Grant, B. & Morris, P. J. Diabetes 33, 1055–1061 (1984).
Adolf, G. R. & Fogy, I. Lymphokine Res. 3, 231–237 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pujol–Borrell, R., Todd, I., Doshi, M. et al. HLA class II induction in human islet cells by interferon-γ plus tumour necrosis factor or lymphotoxin . Nature 326, 304–306 (1987). https://doi.org/10.1038/326304a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/326304a0
This article is cited by
-
Upregulation of HLA class II in pancreatic beta cells from organ donors with type 1 diabetes
Diabetologia (2022)
-
Identification of Critical Transcriptomic Signaling Pathways in Patients with H Syndrome and Rosai-Dorfman Disease
Journal of Clinical Immunology (2021)
-
What the HLA-I!—Classical and Non-classical HLA Class I and Their Potential Roles in Type 1 Diabetes
Current Diabetes Reports (2019)
-
Extracellular Vesicles in Type 1 Diabetes: Messengers and Regulators
Current Diabetes Reports (2019)
-
Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis
The Pharmacogenomics Journal (2017)
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.
