Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease

Gastroenterology. 2015 Nov;149(6):1541-1552.e2. doi: 10.1053/j.gastro.2015.07.013. Epub 2015 Jul 29.

Abstract

Background & aims: Developing antigen-specific approaches for diagnosis and treatment of celiac disease requires a detailed understanding of the specificity of T cells for gluten. The existing paradigm is that T-cell lines and clones from children differ from those of adults in the hierarchy and diversity of peptide recognition. We aimed to characterize the T-cell response to gluten in children vs adults with celiac disease.

Methods: Forty-one children with biopsy-proven celiac disease (median age, 9 years old; 17 male), who had been on strict gluten-free diets for at least 3 months, were given a 3-day challenge with wheat; blood samples were collected and gluten-specific T cells were measured. We analyzed responses of T cells from these children and from 4 adults with celiac disease to a peptide library and measured T-cell receptor bias. We isolated T-cell clones that recognized dominant peptides and assessed whether gluten peptide recognition was similar between T-cell clones from children and adults.

Results: We detected gluten-specific responses by T cells from 30 of the children with celiac disease (73%). T cells from the children recognized the same peptides that were immunogenic to adults with celiac disease; deamidation of peptides increased these responses. Age and time since diagnosis did not affect the magnitude of T-cell responses to dominant peptides. T-cell clones specific for dominant α- or ω-gliadin peptides from children with celiac disease had comparable levels of reactivity to wheat, rye, and barley peptides as T-cell clones from adults with celiac disease. The α-gliadin-specific T cells from children had biases in T-cell receptor usage similar to those in adults.

Conclusions: T cells from children with celiac disease recognize similar gluten peptides as T cells from adults with celiac disease. The findings indicate that peptide-based diagnostics and therapeutics for adults may also be used for children.

Keywords: Food Intolerance Mechanisms; Immune Response; Immunity; Pediatric; T-Cell Epitope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aging / immunology*
  • Celiac Disease / diagnosis*
  • Celiac Disease / immunology*
  • Child
  • Clone Cells / immunology
  • Diet, Gluten-Free
  • Female
  • Glutens / immunology*
  • Humans
  • Male
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • Peptides
  • Receptors, Antigen, T-Cell
  • Glutens