Acta Diabetologica

, Volume 35, Issue 3, pp 137–144

Peptide from glutamic acid decarboxylase similar to coxsackie B virus stimulates IFN-γ mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus

  • M. G. E. Karlsson
  • J. Ludvigsson

DOI: 10.1007/s005920050118

Cite this article as:
Karlsson, M. & Ludvigsson, J. Acta Diabetologica (1998) 35: 137. doi:10.1007/s005920050118


At the clinical onset of insulin-dependent diabetes mellitus (type 1 diabetes), inflammation within the pancreatic islets of Langerhans causes insulitis. CD4+ or Th-lymphocytes will be activated after stimulation resulting in interferon-gamma (IFN-γ) production by Th1-like lymphocytes and/or interleukin-4 (IL-4) secretion from Th2-like lymphocytes. The antigens responsible for this activation are unknown, but studies have suggested glutamic acid decarboxylase (GAD) to be a possible candidate. One peptide from this enzyme (amino acid 247–279) with a similar amino acid sequence to coxsackie B virus may cause lymphocyte proliferation in diabetic patients. In this study we have shown that this peptide activates Th1-like lymphocytes which produce increased amounts of IFN-γ mRNA, but seldom mRNA for IL-4. Lymphocytes from healthy HLA-matched controls (DR3/4) did not respond with an upregulated mRNA expression for these cytokines when stimulated by the GAD-peptide (P<0.05). A low or absent expression of IFN-γ mRNA was significantly correlated to a high fasting C-peptide at 3 months' duration (P<0.05). In conclusion, we suggest that GAD65 is involved in the development of type 1 diabetes and that the Th1-response may play a role in the destruction of β cells.

Key words Th-lymphocytesIFN-γmRNAGAD65coxsackie B virus

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • M. G. E. Karlsson
    • 1
  • J. Ludvigsson
    • 1
  1. 1.Department of Health and Environment, Division of Pediatrics, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, SwedenSE