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Letters to Nature

Nature 326, 304-306 (25 March 1987) | doi:10.1038/326304a0; Received 24 November 1986; Accepted 29 January 1987

HLA class II induction in human islet cells by interferon-big gamma plus tumour necrosis factor or lymphotoxin

Ricardo Pujol–Borrell*, Ian Todd*, Mala Doshi*, Gian Franco Bottazzo*, Robert Sutton†, Derek Gary†, Gunther R. Adolf‡ & Marc Feldmann§

  1. *Immunology Department, Middlesex Hospital Medical School, London W1P 9FG, UK
  2. †Nuffield Department of Surgery, John Radcliffe Hospital, Oxford OX3 9DU, UK
  3. ‡Ernst-Boehringer Institute, A-1121, Vienna, Austria
  4. §Charing Cross Sunley Medical Research Centre, Lurgan Avenue, London W6 8LW, UK
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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-gamma (IFN-gamma)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-gamma in a number of activities8. We report here that IFN-gamma 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.