T cells in peripheral blood after gluten challenge in coeliac disease

Anderson, RP; van Heel, DA; Tye-Din, JA; Barnardo, M; Salio, M; Jewell, DP; Hill, AVS

Author(s): Anderson, RP; van Heel, DA; Tye-Din, JA; Barnardo, M; Salio, M; Jewell, DP; Hill, AVS;
Details: Publication Year 2005-09,Volume 54,Issue #9,Page 1217-1223
Journal Title: GUT
Publication Type: Journal Article
Abstract: Background: Current understanding of T cell epitopes in coeliac disease (CD) largely derives from intestinal T cell clones in vitro. T cell clones allow identification of gluten peptides that stimulate T cells but do not quantify their contribution to the overall gluten specific T cell response in individuals with CD when exposed to gluten in vivo. Aims: To determine the contribution of a putative dominant T cell epitope to the overall gliadin T cell response in HLA-DQ2 CD in vivo. Patients: HLA-DQ2+ individuals with CD and healthy controls. Methods: Subjects consumed 20 g of gluten daily for three days. Interferon gamma (IFN-gamma) ELISPOT was performed using peripheral blood mononuclear cells (PBMC) to enumerate and characterise peptide and gliadin specific T cells before and after gluten challenge. Results: In 50/59 CD subjects, irrespective of homo- or heterozygosity for HLA-DQ2, IFN-gamma ELISPOT responses for an optimal concentration of A-gliadin 57 - 73 Q-E65 were between 10 and 1500 per million PBMC, equivalent to a median 51% of the response for a "near optimal'' concentration of deamidated gliadin. Whole deamidated gliadin and gliadin epitope specific T cells induced in peripheral blood expressed an intestinal homing integrin (alpha 4 beta 7) and were HLA-DQ2 restricted. Peripheral blood T cells specific for A- gliadin 57 - 73 Q-E65 are rare in untreated CD but can be predictably induced two weeks after gluten exclusion. Conclusion: In vivo gluten challenge is a simple safe method that allows relevant T cells to be analysed and quantified in peripheral blood by ELISPOT, and should permit comprehensive high throughput mapping of gluten T cell epitopes in large numbers of individuals with CD.
Publisher: B M J PUBLISHING GROUP
Keywords: SEQUENCE-SPECIFIC PRIMERS; SMALL-INTESTINAL MUCOSA; TISSUE TRANSGLUTAMINASE; RECOGNIZE GLIADIN; PCR-SSP; RESPONSES; LYMPHOCYTES; ACTIVATION; PEPTIDES; TOXICITY
Publisher's Version: https://doi.org/10.1136/gut.2004.059998
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2005-09-01 12:00:00