The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Professor Carolina Ciacci, University Hospital San Giovanni di dio e Ruggi d'Aragona, Italy
- Second opponent: PD Dr. med. Michael Schumann, Charité - University Medicine, Germany
- Third member and chair of the evaluation committee: Associate Professor Stephan Brackmann, University of Oslo
Chair of the Defence
Associate Professor Marianne Klemp, University of Oslo
Principal Supervisor
Professor Knut E. A. Lundin, University of Oslo
Summary
In this thesis we have characterised immunological aspects of coeliac disease; a disorder in which consumption of wheat, barley and rye results in inflammation of the gut. It is known that coeliac disease patients have so-called gluten-specific CD4+ T cells in blood and gut and that these cells are present even if the coeliacs follow a gluten-free diet. It is also known that three days with gluten-containing food result in a numerical increase of gluten-specific cells in blood on the 6. day after re-introduction of gluten.
The studies of this thesis focused on important aspects of those gluten-specific CD4+ T cells in blood. We found that numbers of gluten-specific T cells that expressed the cell surface marker CD38 increased in all participants. Compared to other potential outcome measures we studied, expression of CD38 by gluten-specific T cells stands out as a promising alternative to contemporary measures for monitoring of immune activation in clinical trials of new coeliac drugs.
Further we studied genes which are switched on in gluten-specific T cells in the context of antigen induced activation. Transcriptome analysis revealed over 3000 affected genes, among them 94 genes coding for cell surface markers. Those were studied further with so-called mass cytometry, a method that allows for simultaneous staining of many cell markers. We found a relevant overlap of cell characteristics of gluten-specific T cells in blood induced by gluten challenge compared with the small intestine. Studies of gluten-specific T cells in blood may therefore provide relevant immunological information in 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 activation of gluten-specific CD4+ T cells likely causes expansion of CD8+ αβ or γδ T cells. These latter cells express highly diverse T-cell receptors indicating that they probably do not recognise gluten.
Additional information
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