Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes

P. Panina-Bordignon, R. Lang, P. M. Van Endert, E. Benazzi, A. M. Felix, R. M. Pastore, G. A. Spinas, F. Sinigaglia

Research output: Contribution to journalArticlepeer-review

Abstract

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results in the destruction of the pancreatic islet β cells. Glutamic acid decarboxylase (GAD) has been recently indicated as a key autoantigen in the induction of IDDM in nonobese diabetic mice. In human diabetes, the mechanism by which the β cells are destroyed is still unknown. Here we report the first evidence for the presence of GAD-specific cytotoxic T cells in asymptomatic and recent diabetic patients. GAD65 peptides displaying the human histocompatibility leukocyte antigen (HLA)-A*0201 binding motif have been synthesized. One of these peptides, GAD114-123, binds to HLA-A*0201 molecules in an HLA assembly assay. Peripheral blood mononuclear cells from individuals with preclinical IDDM, recent-onset IDDM, and from healthy controls were stimulated in vitro with the selected peptide in the presence of autologous antigen-presenting cells. In three cases (one preclinical IDDM and two recent-onset IDDM), we detected specific killing of autologous antigen-presenting cells when incubated with GAD114-123 peptide or when infected with a recombinant vaccinia virus expressing GAD65. These patients were the only three carrying the HLA-A*0201 allele among the subjects studied. Our finding suggests that GAD-specific cytotoxic T lymphocytes may play a critical role in the initial events of IDDM.

Original languageEnglish
Pages (from-to)1923-1927
Number of pages5
JournalJournal of Experimental Medicine
Volume181
Issue number5
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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