Gliadin-reactive T cells in Italian children from preventCD cohort at high risk of celiac disease

Pediatr Allergy Immunol. 2017 Jun;28(4):362-369. doi: 10.1111/pai.12720.


Background: Newborns at high risk of celiac disease (CD) were recruited in Italy in the context of the PreventCD study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T-cell reactivity to gliadin at the first clinical and/or serological signs of CD.

Methods: Gliadin-reactive T-cell lines were generated from intestinal biopsies of 19 HLA-DQ2-or HLA-DQ8-positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls. Immune reactivity was evaluated against gliadin and known immunogenic peptides from α-, γ-, or ω-gliadins. The role of deamidation by transglutaminase (tTG) in determining the immunogenicity of gliadin was also investigated.

Results: Most of the children with CD (either acute or potential) had an inflammatory response to gliadin. Notably, signs of T-cell reactivity to gliadin were also found in some non-celiac subjects, in which IFN-γ responses occurred mainly when regulatory IL-10 and TGF-β cytokines were blocked. Interestingly, PreventCD children reacted to gliadin peptides found active in adult CD patients, and tTG deamidation markedly enhanced gliadin recognition.

Conclusions: T cells reactive to gliadin can be detected in the intestine of children at high risk of developing CD, in some cases also in the presence of a normal mucosa and negative CD-associated antibodies. Furthermore, children at a very early stage of CD recognize the same gliadin epitopes that are active in adult CD patients. Tissue transglutaminase strongly enhances gluten T-cell immunogenicity in early CD.

Keywords: antigluten T-cell lines; celiac disease; children at genetic risk; early gut immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / immunology
  • Celiac Disease / immunology*
  • Cell Line
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gliadin / immunology*
  • Humans
  • Hypersensitivity / immunology*
  • Infant
  • Italy
  • Lymphocyte Activation
  • Male
  • Risk
  • T-Lymphocytes / immunology*


  • Antigens
  • Gliadin