Gluten challenge in coeliac disease: Analysis of gluten-specific T cells in blood

Abstract

In this thesis, we have worked on an immunological feature, which is characteristic for patients with coeliac disease; a disease, in which consumption of wheat, barley and rye results in inflammation of the gut. We found that expression of the cell surface marker CD38 on gluten-specific T cells increased in all participants. Compared to other potential outcome measures, CD38 stands out as a possible alternative to contemporary measures for immune activation in clinical trials. We also studied the genes, which are switched on in the context of immune activation and found a relevant overlap of cell characteristics of gluten-specific T cells in blood compared to the small intestine. This lets us assume that gluten-specific T cells in blood are a valid estimate of cells in the small intestine. Gluten-specific CD4+ T cells may therefore serve as an immunological read-out for clinical drug trials. We also tested the hypothesis that not only CD4+ T cells, but also CD8+ αβ and γδ T cells show a response to gluten challenge. We found that it is most likely that CD4+ T cells initiate expansion of CD8+ αβ or γδ T cells, but that the latter are unlikely to recognise gluten on their own.