Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans

T Mandrup-Poulsen, K Bendtzen, J Nerup, J Egeberg, Jens Høiriis Nielsen

57 Citations (Scopus)

Abstract

Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet contents of insulin and glucagon in a dose-dependent manner. A maximal effect on islet function was obtained with supernatant concentrations down to 5%. Supernatants of mononuclear cells stimulated with tuberculin were more potent than supernatants produced by lectin stimulation. Culture medium reconstituted with tuberculin or phytohaemagglutinin did not impair islet function. Electron microscopy demonstrated that supernatants were cytotoxic to islet cells. The cytotoxic mononuclear cell mediator(s) was non-dialysable, sensitive to heating to 56 degrees C, labile even when stored at -70 degrees C, but stable when lyophilised.
Original languageEnglish
JournalAllergy
Volume41
Issue number4
Pages (from-to)250-9
Number of pages10
ISSN0105-4538
Publication statusPublished - May 1986

Keywords

  • Animals
  • Autoimmune Diseases
  • Biological Agents
  • Cytokines
  • Cytotoxicity, Immunologic
  • Diabetes Mellitus, Type 1
  • Dose-Response Relationship, Immunologic
  • Humans
  • Insulin
  • Islets of Langerhans
  • Leukocytes
  • Male
  • Phytohemagglutinins
  • Rats
  • Rats, Inbred Strains
  • Tuberculin

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