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

Clin Exp Immunol. 2012 May;168(2):207-14. doi: 10.1111/j.1365-2249.2012.04575.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Celiac Disease / diagnosis
  • Celiac Disease / immunology*
  • Celiac Disease / metabolism
  • Child
  • Child, Preschool
  • Epitopes / immunology
  • Female
  • Gliadin / chemistry
  • Gliadin / immunology*
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Integrin beta Chains / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Phenotype

Substances

  • Epitopes
  • Integrin beta Chains
  • integrin beta7
  • Gliadin