TY - JOUR
T1 - Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease
AU - Maiuri, Luigi
AU - Ciacci, Carolina
AU - Ricciardelli, Ida
AU - Vacca, Loredana
AU - Raia, Valeria
AU - Auricchio, Salvatore
AU - Picard, Jean
AU - Osman, Mohamed
AU - Quaratino, Sonia
AU - Londei, Marco
PY - 2003/7/5
Y1 - 2003/7/5
N2 - Background: The adaptive immune system is central to the development of coeliac disease. Adaptive immune responses are, however, controlled by a preceding activation of the innate immune system. We investigated whether gliadin, a protein present in wheat flour, could activate an innate as well as an adaptive immune response in patients with coeliac disease. Methods: Duodenal biopsy samples from 42 patients with untreated coeliac disease, 37 treated patients, and 18 controls, were cultured in vitro for 3 h or 24 h, in the presence of either immunodominant gliadin epitopes (pα-2 and pα-9) or a non-immunodominant peptide (p31-43) known to induce small intestine damage in coeliac disease. We also incubated biopsy samples from nine untreated and six treated patients with a non-immunodominant peptide for 3 h, before incubation with immunodominant gliadin epitopes. Different combinations of interleukin-15 or signal transduction inhibitors were added to selected incubations. Findings: Only the non-immunodominant peptide induced rapid expression of interleukin-15, CD83, cyclo-oxygenase (COX)-2, and CD25 by CD3- cells (p=0.005 vs medium alone) and enterocyte apoptosis (p
AB - Background: The adaptive immune system is central to the development of coeliac disease. Adaptive immune responses are, however, controlled by a preceding activation of the innate immune system. We investigated whether gliadin, a protein present in wheat flour, could activate an innate as well as an adaptive immune response in patients with coeliac disease. Methods: Duodenal biopsy samples from 42 patients with untreated coeliac disease, 37 treated patients, and 18 controls, were cultured in vitro for 3 h or 24 h, in the presence of either immunodominant gliadin epitopes (pα-2 and pα-9) or a non-immunodominant peptide (p31-43) known to induce small intestine damage in coeliac disease. We also incubated biopsy samples from nine untreated and six treated patients with a non-immunodominant peptide for 3 h, before incubation with immunodominant gliadin epitopes. Different combinations of interleukin-15 or signal transduction inhibitors were added to selected incubations. Findings: Only the non-immunodominant peptide induced rapid expression of interleukin-15, CD83, cyclo-oxygenase (COX)-2, and CD25 by CD3- cells (p=0.005 vs medium alone) and enterocyte apoptosis (p
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U2 - 10.1016/S0140-6736(03)13803-2
DO - 10.1016/S0140-6736(03)13803-2
M3 - Article
C2 - 12853196
AN - SCOPUS:0038501062
VL - 362
SP - 30
EP - 37
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9377
ER -