Gliadin Activates HLA Class I-restricted CD8+ T Cells in Celiac Disease Intestinal Mucosa and Induces the Enterocyte Apoptosis

Overview

Journal Gastroenterology

Specialty Gastroenterology

Date 2008 Apr 9

PMID 18395083

Citations 33

Authors

Giuseppe Mazzarella

Rosita Stefanile

Alessandra Camarca

Paolo Giliberti

Elena Cosentini

Caterina Marano

Gaetano Iaquinto

Nicola Giardullo

Salvatore Auricchio

Alessandro Sette

Riccardo Troncone

Carmen Gianfrani

Affiliations

Soon will be listed here.

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.

Citing Articles

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Camarca A, Rotondi Aufiero V, Mazzarella G Int J Mol Sci. 2023; 24(19).

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