Details

Autor(en) / Beteiligte

• Steenholt, Janni V
• Nielsen, Christian
• Baudewijn, Leen
• Staal, Anne
• Rasmussen, Karina S
• Sabir, Hardee J
• Barington, Torben
• Husby, Steffen
• Toft-Hansen, Henrik
• Crispin, Jose C.

Titel

The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients

Ist Teil von

• PloS one, 2017-02, Vol.12 (2), p.e0170270-e0170270

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+) and the number of CD3+ CD4- CD8- double-negative (DN) T cells were elevated 6-7 fold in children with CD. We next isolated and quantified intraepithelial lymphocytes (IELs) from biopsies obtained from patients (both children and adults) with CD, potential CD and non-CD controls. Flow cytometric analysis of the duodenal T cell subpopulations was performed including the markers TCRαβ, TCRγδ, CD4, CD8α and CD8β. Proportions of γδ T cells and CD8αβ+ cells among IELs were increased in CD patients, whereas proportions of CD4+ CD8αα+ and CD4+ single-positive T cells were decreased. Additionally, two gluten-reactive T cell lines (TCLs) derived from CD biopsies were analyzed for changes in proportions of T cell subsets before and after gluten stimulation. In a proliferation assay, dividing cells were tracked with carboxyfluorescein succinimidyl ester (CFSE), and both αβ and γδ T cells proliferated in response to gluten. Changes in duodenal T cell subpopulations in potential CD patients followed the same pattern as for CD patients, but with less pronounced effect.