High T cell responses to the glutamic acid decarboxylase (GAD) isoform 67 reflect a hyperimmune state that precedes the onset of insulin-dependent diabetes

Journal of Autoimmunity
M C HoneymanL C Harrison

Abstract

Pancreatic islet beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is an autoimmune T cell-mediated process. Peripheral blood T cells, which proliferate to islet antigens such as glutamic acid decarboxylase (GAD), (pro)insulin or tyrosine phosphatase IA-2, can be detected in at-risk, first degree relatives of people with IDDM. However, cross-sectional studies cannot define the relationship between T cell responses and progression to IDDM. Longitudinal studies were therefore undertaken on 50 at-risk, first degree relatives tested at least yearly for up to 4 years, during which time five developed IDDM. Peripheral blood T cell responses to a GAD67(aa208-404)-glutathione-S-transferase (GST) fusion protein, GST, insulin and tetanus toxoid were measured, together with antibodies to islet cells, GAD, insulin and IA-2. High levels of antibodies to GAD or insulin were generally associated with low T cell responses to these antigens. Relatives who developed IDDM were characterized by high levels of antibodies to insulin and/or islet cells, and high T cell responses to GAD67-GST and tetanus, but not insulin, in the 24 months before clinical diagnosis. Cross-sectionally, T cell responses to GAD67(aa208-404)-GST a...Continue Reading

Citations

Jan 9, 2008·Immunology and Cell Biology·Leonard C Harrison
Aug 3, 2002·Immunology·Nikolai PetrovskyLeonard C Harrison
Mar 16, 2004·Pediatric Diabetes·L C Harrison
Nov 5, 1997·Diabetologia·M HoneymanA Rossini
Dec 9, 2003·Journal of Immunological Methods·Stuart I ManneringLeonard C Harrison
Feb 9, 2005·Annals of the New York Academy of Sciences·Stuart I ManneringLeonard C Harrison
Aug 21, 2001·CNS Drugs·H M Meinck
Apr 10, 2010·International Journal of Immunopathology and Pharmacology·R CiccocioppoG R Corazza

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