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


METHODS
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.


CONCLUSIONS
In vitro, p10mer showed the ability to shift the pathogenic immune response of a CD patient from a Th1- to a Th2-type response.
Silano
Marco
M
Division of Food Science, Human Nutrition and Health, Istituto Superiore di Sanità, Rome, Italy.
Di Benedetto
Rita
R
Maialetti
Francesca
F
De Vincenzi
Alessandro
A
Calcaterra
Roberta
R
Trecca
Antonello
A
De Vincenzi
Massimo
M
D000293:Adolescent; D002446:Celiac Disease / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014908:Triticum / Q000276:immunology*
D016207:Cytokines; D009842:Oligopeptides; D016753:Interleukin-10; D007371:Interferon-gamma; D005903:Gliadin