A 10-residue peptide from durum wheat promotes a shift from a Th1-type response toward a Th2-type response in celiac disease

Am J Clin Nutr. 2008 Feb;87(2):415-23. doi: 10.1093/ajcn/87.2.415.

Abstract

Background: Celiac disease (CD) is a Th1-driven autoimmune permanent enteropathy that is triggered by dietary gluten. Molecules able to shift the immune response from a Th1- to a Th2-type response have been suggested as therapeutic agents for Th1 autoimmune diseases.

Objective: We sought to investigate the possibility that a decapeptide from durum wheat (p10mer, QQPQDAVQPF), which was previously shown to prevent the activation of celiac peripheral lymphocytes, may promote a shift from a Th1- to a Th2-type immune response in gluten-specific intestinal T cells of CD patients.

Design: Intestinal T lymphocyte lines derived from 8 children with CD were incubated with gliadin peptides both alone and simultaneously with p10mer. Cell proliferation and the production of interferon-gamma and interleukin-10 by these T cells were measured.

Results: The incubation of celiac intestinal T cells with deamidated gliadin peptides resulted in a significant (P < 0.008) increase in cell proliferation and interferon-gamma release, whereas the simultaneous exposure to p10mer totally abolished the cell proliferation and cytokine release. Moreover, incubation with p10mer maintained an elevated release of interleukin-10, whereas exposure of the cells to culture medium only did not. The replacement of the residues of aspartic acid in position 5 or those of alanine in position 6 in the sequence of p10mer resulted in peptides with no activity in the activation experiments.

Conclusion: In vitro, p10mer showed the ability to shift the pathogenic immune response of a CD patient from a Th1- to a Th2-type response.

MeSH terms

  • Adolescent
  • Celiac Disease / immunology*
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cytokines / metabolism*
  • Female
  • Gliadin / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Male
  • Oligopeptides / immunology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Triticum / immunology*

Substances

  • Cytokines
  • Oligopeptides
  • Interleukin-10
  • Interferon-gamma
  • Gliadin