title: Increased peripheral blood CD4+ T cell responses to deamidated but not to native gliadin in children with coeliac disease.
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.
authors.affiliation: Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland. anne.lammi@uef.fi
authors.forename: A
authors.initials: A
authors.lastname: Lammi
authors.forename: P
authors.initials: P
authors.lastname: Arikoski
authors.forename: O
authors.initials: O
authors.lastname: Vaarala
authors.forename: T
authors.initials: T
authors.lastname: Kinnunen
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000276:immunology; D005260:Female; D005903:Gliadin / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D039641:Integrin beta Chains / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010641:Phenotype
chemical_list: D000939:Epitopes; D039641:Integrin beta Chains; C091368:integrin beta7; D005903:Gliadin