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
1998 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 35, no 3, 137-144 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
1998. Vol. 35, no 3, 137-144 p.
Th-lymphocytes, IFN-γ, mRNA, GAD65, coxsackie B virus
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-79851DOI: 10.1007/s005920050118PubMedID: 9840449OAI: oai:DiVA.org:liu-79851DiVA: diva2:544410