Digital Public Defence: Linn Margrethe Eggesbø
MSc Linn Margrethe Eggesbø at Institute of Clinical Medicine will be defending the thesis On the γδ and CD8+ αβ T-cell receptor repertoires in coeliac disease for the degree of PhD (Philosophiae Doctor).
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.
Digital Trial Lecture – time and place
- First opponent: Docent Päivi Saavalainen, University of Helsinki, Finland
- Second opponent: Professor Michael Uhlin, Karolinska Institutet, Sweden
- Third member and chair of the evaluation committee: Professor Erik Dissen, University of Oslo
Chair of the Defence
Professor II Inger Nina Farstad, University of Oslo
Professor Ludvig M. Sollid, University of Oslo
Coeliac disease is an inflammatory disease of the small intestine that is caused by dietary gluten. Currently, the only available treatment for coeliac disease is a gluten-free diet. In coeliac disease there is an increase of intraepithelial lymphocytes (IELs) in the small intestine of patients. These IELs are mainly T cells harbouring an αβ or γδ T-cell receptor (TCR) with unknown specificity. The CD8+ αβ IELs are thought to participate in tissue destruction in coeliac disease whereas the role of γδ IELs is less defined. Notably, the frequency of gut-homing γδ and CD8+ αβ T cells in blood increase when patients eat gluten.
In this thesis we have sequenced the TCR genes of both γδ and CD8+ αβ IELs in treated and untreated patients and compared their TCR repertoires with controls. We found that the γδ TCR repertoire in untreated patients was changed in comparison to controls and that the treated patients are very similar, with significant changes in V-gene usage. Contrastingly, we show that there is no V-gene bias in CD8+ αβ IELs compared with controls. We demonstrate that the TCR diversity is increased in coeliac disease, in both γδ and CD8+ αβ IELs.
Additionally, we also sequenced the TCR repertoires of γδ and CD8+ αβ T cells from the blood and intestine in patients undergoing a gluten challenge for 14 days. We show that we can find the same γδ or CD8+ αβ clonotypes in the blood as in the intestine, which has not been reported previously.
The work presented in this thesis contributes new insights into the composition of these γδ and CD8+ αβ T cells in coeliac disease, and will be a platform for further clarification of their roles in the disease.
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