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.
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 Th1autoimmune 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 CDpatients. 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 CDpatient from a Th1- to a Th2-type response.
Authors: Henry J McSorley; Soraya Gaze; James Daveson; Dianne Jones; Robert P Anderson; Andrew Clouston; Nathalie E Ruyssers; Richard Speare; James S McCarthy; Christian R Engwerda; John Croese; Alex Loukas Journal: PLoS One Date: 2011-09-16 Impact factor: 3.240