Islet T cells secreting IFN-gamma in NOD mouse diabetes: arrest by p277 peptide treatment

J Autoimmun. 1998 Feb;11(1):73-81. doi: 10.1006/jaut.1997.0177.


Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent (type 1) diabetes mellitus (IDDM) caused by T cells which destroy the insulin-producing islet beta-cells. Since cytokines are involved in this auto-immune beta-cell damage, we used an ELISPOT assay to enumerate the islet-associated T cells that secreted interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). We used mitogenic anti-CD3 antibody to activate all the T cells capable of responding, irrespective of their antigen specificity. We found that NOD females, more susceptible than males to IDDM, accumulated islet IFN-gamma producers more rapidly with age than did the males. Acceleration of male IDDM by cyclophosphamide led to a marked increase in IFN-gamma secreting islet T cells. In contrast, a decrease in IFN-gamma-producing islet T cells was associated with arrest of IDDM by administration of peptide p277 of the 60 kDa heat-shock protein (hsp60) to 12-week-old female NOD mice. The p277-treated mice later manifested a greater number of islets and fewer leukocytes per islet than did the mice treated with a bacterial hsp60 peptide. Thus, the development of diabetes could be correlated with the accumulation in the islets of T cells producing IFN-gamma, and destructive insulitis could be downregulated by the administration of a single peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amino Acid Sequence
  • Animals
  • Calibration
  • Chaperonin 60
  • Cyclophosphamide / pharmacology
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy*
  • Enzyme-Linked Immunosorbent Assay / standards
  • Female
  • Heat-Shock Proteins / therapeutic use*
  • Interferon Inducers / pharmacology
  • Interferon-gamma / drug effects
  • Interferon-gamma / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Molecular Sequence Data
  • Peptide Fragments / therapeutic use*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • Chaperonin 60
  • Cytokines
  • Heat-Shock Proteins
  • Interferon Inducers
  • Peptide Fragments
  • peptide 277, heat shock protein 60
  • Interferon-gamma
  • Cyclophosphamide