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Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease
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 im...
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Published in: | The Lancet (British edition) 2003-07, Vol.362 (9377), p.30-37 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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.
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.
Only the non-immunodominant peptide induced rapid expression of interleukin-15,
cd83
, cyclo-oxygenase (COX)-2, and CD25 by CD3– cells (p=O005 vs medium alone) and enterocyte apoptosis (p |
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ISSN: | 0140-6736 1474-547X |
DOI: | 10.1016/S0140-6736(03)13803-2 |