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Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease


Hardy, MY; Girardin, A; Pizzey, C; Cameron, DJ; Watson, KA; Picascia, S; Auricchio, R; Greco, L; Gianfrani, C; La Gruta, NL; Anderson, RP; Tye-Din, JA
2015-11
2015-07-27
Gastroenterology
Journal Article
149
6
1541-1552
BACK GROUND AND AIMS: Developing antigen-specific approaches for diagnosis and treatment of celiac disease requires a detailed understanding of the specificity of T cells for gluten. The existing paradigm is that T-cell lines and clones from children differ from those of adults in the hierarchy and diversity of peptide recognition. We aimed to characterize the T-cell response to gluten in children vs adults with celiac disease. METHODS: Forty-one children with biopsy-proven celiac disease (median age, 9 y; 17 male), who had been on strict gluten-free diets for at least 3 months, were given a 3 day challenge with wheat; blood samples were collected and gluten-specific T cells were measured. We analyzed responses of T cells from these children and from 4 adults with celiac disease to a peptide library and measured T-cell receptor bias. We isolated T-cell clones that recognized dominant peptides and assessed whether gluten peptide recognition was similar between T-cell clones from children and adults. RESULTS: We detected gluten-specific responses by T cells from 30 of the children with celiac disease (73%). T cells from the children recognized the same peptides that were immunogenic to adults with celiac disease; deamidation of peptides increased these responses. Age and time since diagnosis did not affect the magnitude of T-cell responses to dominant peptides. T-cell clones specific for dominant alpha- or omega-gliadin peptides from children with celiac disease had comparable levels of reactivity to wheat, rye, and barley peptides as T-cell clones from adults with celiac disease. The alpha-gliadin-specific T cells from children had biases in T-cell receptor usage similar to those of adults. CONCLUSIONS: T cells from children with celiac disease recognize similar gluten peptides as T cells from adults with celiac disease. The findings indicate that peptide-based diagnostics and therapeutics for adults may also be used for children.
Elsevier
Immunology
10.1053/j.gastro.2015.07.013
26226573
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Creation Date 2015-10-28 03:35:35 Last Modified 2015-11-24 03:28:00