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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Gliadin activates HLA Class I-restricted CD8+ T-cells in coeliac intestinal mucosa and induces the enterocyte apoptosis.
Anno di pubblicazione: 2008
Autori: Mazzarella G, Stefanile R, Camarca A, Giliberti P, Casentini E, Marano C, Iaquinto G, Giardullo N, Auricchio S, Sette A, Troncone R, Gianfrani C.
Affiliazioni autori: Institute of Food Sciences, CNR, Avellino, Italy; ?Immunohematology and Transfusion Medicin and §European Laboratory for the Investigation of Food-Induced Diseases, University of Naples Federico II, Naples, Italy; Gastroenterology Unit, Hospital Moscati, Avellino, Italy; and śLa Jolla Institute for Allergy and Immunology, San Diego, California
Abstract: BACKGROUND & AIMS: The extensive infiltration of CD8(+) T cells in the intestinal mucosa of celiac disease (CD) patients is a hallmark of the disease. We identified a gliadin peptide (pA2) that is selectively recognized by CD8(+) T cells infiltrating intestinal mucosa of HLA-A2(+) CD patients. Herein, we investigated the phenotype, the tissue localization, and the effector mechanism of cells responsive to pA2 by using the organ culture of CD intestinal mucosa. The target of pA2-mediated cytotoxicity was also investigated by using the intestinal epithelial cell lines Caco2 and HT29, A2(+) and A2(-), respectively, as target cells. METHODS: Jejunal biopsy specimens from CD patients were cultured in vitro with pA2, and cellular activation was evaluated by immunohistochemistry and cytofluorimetric analysis. Cytotoxicity of pA2-specific, intestinal CD8(+) T cells was assayed by granzyme-B and interferon-gamma release and by apoptosis of target cells. RESULTS: pA2 challenge of A2(+) CD mucosa increased the percentage of CD8(+)CD25(+) and of CD80(+) cells in the lamina propria, the former mainly localized beneath the epithelium, as well as the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-positive cells (TUNEL(+)) in the epithelium. Intraepithelial CD3(+) cells and enterocyte expression of Fas were also increased. CD8(+)CD25(+) and CD8(+)FASL(+) T cells were significantly increased in cell preparations from biopsy specimens cultured with pA2. CD8(+) T-cell lines released both granzyme-B and interferon-gamma following recognition of pA2 when presented by Caco2 and not by HT29. CONCLUSIONS: These data indicate that gliadins contain peptides able to activate, through a TCR/HLA class I interaction, CD8-mediated response in intestinal CD mucosa and to induce the enterocyte apoptosis.
Lingua abstract: inglese
Pagine da: 1017
Pagine a: 1027
Numero volume: 134
Indicizzato da: ISI Web of Science (WOS) 
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