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T cells in peripheral blood after gluten challenge in coeliac disease.
Gut. 2005 Sep; 54(9):1217-23.Gut

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 (alpha4beta7) 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.

Authors+Show Affiliations

Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, c/o Post Office RMH, Victoria, Australia 3050. banderson@wehi.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16099789

Citation

Anderson, R P., et al. "T Cells in Peripheral Blood After Gluten Challenge in Coeliac Disease." Gut, vol. 54, no. 9, 2005, pp. 1217-23.
Anderson RP, van Heel DA, Tye-Din JA, et al. T cells in peripheral blood after gluten challenge in coeliac disease. Gut. 2005;54(9):1217-23.
Anderson, R. P., van Heel, D. A., Tye-Din, J. A., Barnardo, M., Salio, M., Jewell, D. P., & Hill, A. V. (2005). T cells in peripheral blood after gluten challenge in coeliac disease. Gut, 54(9), 1217-23.
Anderson RP, et al. T Cells in Peripheral Blood After Gluten Challenge in Coeliac Disease. Gut. 2005;54(9):1217-23. PubMed PMID: 16099789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cells in peripheral blood after gluten challenge in coeliac disease. AU - Anderson,R P, AU - van Heel,D A, AU - Tye-Din,J A, AU - Barnardo,M, AU - Salio,M, AU - Jewell,D P, AU - Hill,A V S, PY - 2005/8/16/pubmed PY - 2005/12/13/medline PY - 2005/8/16/entrez SP - 1217 EP - 23 JF - Gut JO - Gut VL - 54 IS - 9 N2 - 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 (alpha4beta7) 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. SN - 0017-5749 UR - https://www.unboundmedicine.com/medline/citation/16099789/T_cells_in_peripheral_blood_after_gluten_challenge_in_coeliac_disease_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=16099789 DB - PRIME DP - Unbound Medicine ER -