Detection of GAD65 autoreactive t-cells by HLA class i tetramers in type 1 diabetic patients

Alessandra Fierabracci, Laura Giuliani, Raffaella Mele, Monica Di Giovine, Laura Altieri, Antonino Crinó, Lucilla Ravá

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Type 1 diabetes (T1D) is an autoimmune disease, in which pancreatic cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies.

Original languageEnglish
Article number576219
JournalJournal of Biomedicine and Biotechnology
Volume2009
DOIs
Publication statusPublished - 2009

Fingerprint

Glutamate Decarboxylase
Autoantigens
Protein Isoforms
Type 1 Diabetes Mellitus
Peptides
Lymphocytes
T-Lymphocytes
Cytotoxic T-Lymphocytes
Autoantibodies
Autoimmune Diseases
Epitopes

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Detection of GAD65 autoreactive t-cells by HLA class i tetramers in type 1 diabetic patients. / Fierabracci, Alessandra; Giuliani, Laura; Mele, Raffaella; Di Giovine, Monica; Altieri, Laura; Crinó, Antonino; Ravá, Lucilla.

In: Journal of Biomedicine and Biotechnology, Vol. 2009, 576219, 2009.

Research output: Contribution to journalArticle

@article{0ccccac7b74e499abc9cfc392fe19abe,
title = "Detection of GAD65 autoreactive t-cells by HLA class i tetramers in type 1 diabetic patients",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease, in which pancreatic cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies.",
author = "Alessandra Fierabracci and Laura Giuliani and Raffaella Mele and {Di Giovine}, Monica and Laura Altieri and Antonino Crin{\'o} and Lucilla Rav{\'a}",
year = "2009",
doi = "10.1155/2009/576219",
language = "English",
volume = "2009",
journal = "Journal of Biomedicine and Biotechnology",
issn = "1110-7243",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Detection of GAD65 autoreactive t-cells by HLA class i tetramers in type 1 diabetic patients

AU - Fierabracci, Alessandra

AU - Giuliani, Laura

AU - Mele, Raffaella

AU - Di Giovine, Monica

AU - Altieri, Laura

AU - Crinó, Antonino

AU - Ravá, Lucilla

PY - 2009

Y1 - 2009

N2 - Type 1 diabetes (T1D) is an autoimmune disease, in which pancreatic cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies.

AB - Type 1 diabetes (T1D) is an autoimmune disease, in which pancreatic cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies.

UR - http://www.scopus.com/inward/record.url?scp=73449127210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73449127210&partnerID=8YFLogxK

U2 - 10.1155/2009/576219

DO - 10.1155/2009/576219

M3 - Article

VL - 2009

JO - Journal of Biomedicine and Biotechnology

JF - Journal of Biomedicine and Biotechnology

SN - 1110-7243

M1 - 576219

ER -