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“T cell recognition of gliadin from dietary gluten is essential for the pathogenesis of coeliac disease (CD). The aim of the present study was to analyse whether gliadin-specific T cells are detectable in the circulation of children with newly diagnosed coeliac disease by using a sensitive carboxfluorescein diacetate succinimidyl ester (CFSE)

dilution method. Peripheral blood CD4+ T cell responses were analysed in 20 children at diagnosis of CD and compared to those in 64 healthy control children carrying the CD-associated Olaparib human leucocyte antigen (HLA)-DQ2 or -DQ8 alleles. Deamidated gliadin (gTG)-specific T cells were detectable in the peripheral blood of more than half the children with CD (11 of 20, 55%) compared to 15 of 64 (23·4%) of the control children (P = 0·008). Proliferative responses to gTG were also significantly stronger in children with CD than in controls (P = 0·01). In contrast, T cells specific to

native gliadin were detectable at comparable frequencies in children with CD (two of 19, 10·5%) and controls (13 of 64, 20·3%). gTG-specific T cells had a memory phenotype more Apitolisib cell line often than those specific to native gliadin in children with CD (P = 0·02), whereas controls had similar percentages of memory cells in both stimulations. Finally, gTG-specific CD4+ T cells had a higher expression of the gut-homing molecule β7 integrin than those specific to the control antigen tetanus toxoid. Collectively, our current

results demonstrate that the frequency of circulating memory CD4+ T cells specific to gTG but not native gliadin is increased in children with newly diagnosed CD. Coeliac disease (CD) is a T cell-mediated chronic inflammatory disorder of the small intestine, and is mediated by intestinal T cells that recognize peptide epitopes of gluten in the context of disease-associated human leucocyte antigen for (HLA)-DQ molecules [1,2]. The highest risk for CD is associated with the presence of the DQ2 molecule, encoded by the DQA1*05 and DQB1*02 alleles [3]. More than 90% of patients are positive for HLA-DQ2, and most of those without DQ2 express the DQ8 molecule, encoded by the DQA1*03 and DQB1*0302 alleles [3]. In the gut mucosa, ingested oral gluten is deamidated by tissue transglutaminase (TTG). In turn, this deamidation enhances the immunogenicity of gluten by increasing the affinity between deamidated gliadin (gTG) epitopes and DQ2 and DQ8 molecules [4–6]. Gluten-specific T cell responses have been studied mainly on lymphocytes from small intestine biopsy samples [1,5,7–9], but they can also be detected in the peripheral blood. The frequency of these specific T cells in the circulation of CD patients is low, and studies have been performed mainly after oral gluten challenge in order to increase the number of circulating gliadin-specific cells in vivo[10–12].