Increased peripheral blood CD4 + T cell responses to deamidated but not to native gliadin in children with coeliac disease

Summary 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 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 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.