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 journalArticle

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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

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Glutamate Decarboxylase
Type 1 Diabetes Mellitus
Histocompatibility Antigens
T-Lymphocytes
HLA Antigens
Autoantigens
Peptides
Antigen-Presenting Cells
Islets of Langerhans
Inbred NOD Mouse
Vaccinia virus
Cytotoxic T-Lymphocytes
Autoimmune Diseases
Blood Cells
Alleles

ASJC Scopus subject areas

  • Immunology

Cite this

Panina-Bordignon, P., Lang, R., Van Endert, P. M., Benazzi, E., Felix, A. M., Pastore, R. M., ... Sinigaglia, F. (1995). Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. Journal of Experimental Medicine, 181(5), 1923-1927.

Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. / Panina-Bordignon, P.; Lang, R.; Van Endert, P. M.; Benazzi, E.; Felix, A. M.; Pastore, R. M.; Spinas, G. A.; Sinigaglia, F.

In: Journal of Experimental Medicine, Vol. 181, No. 5, 1995, p. 1923-1927.

Research output: Contribution to journalArticle

Panina-Bordignon, P, Lang, R, Van Endert, PM, Benazzi, E, Felix, AM, Pastore, RM, Spinas, GA & Sinigaglia, F 1995, 'Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes', Journal of Experimental Medicine, vol. 181, no. 5, pp. 1923-1927.
Panina-Bordignon P, Lang R, Van Endert PM, Benazzi E, Felix AM, Pastore RM et al. Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. Journal of Experimental Medicine. 1995;181(5):1923-1927.
Panina-Bordignon, P. ; Lang, R. ; Van Endert, P. M. ; Benazzi, E. ; Felix, A. M. ; Pastore, R. M. ; Spinas, G. A. ; Sinigaglia, F. / Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. In: Journal of Experimental Medicine. 1995 ; Vol. 181, No. 5. pp. 1923-1927.
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