Gluten challenge in coeliac disease: Analysis of gluten-specific T cells in blood
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- Institutt for klinisk medisin [10714]
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.List of papers
Paper I: CD38 expression on gluten-specific T cells is a robust marker of gluten re-exposure in coeliac disease. Stephanie Zühlke, Louise Fremgaard Risnes, Shiva Dahal-Koirala, Asbjørn Christophersen, Ludvig M. Sollid and Knut E.A. Lundin. United European Gastroenterology Journal, 7(10), 1337–1344. DOI: 10.1177/2050640619874183. The article is included in the thesis. Also available at: https://doi.org/10.1177/2050640619874183 |
Paper II: Gluten-specific CD4+ T cells express a distinct set of markers after gluten challenge that correlate well on the transcriptomic and phenotypic level. Stephanie Zühlke, Asbjørn Christophersen, Eivind Gard Lund, Omri Snir, Louise Fremgaard Risnes, Shiva Dahal-Koirala, Linn Eggesbø, Ludvig M. Sollid and Knut E.A. Lundin. Manuscript. To be published. The paper is not available in DUO awaiting publishing. |
Paper III: Circulating CD103+ γδ and CD8+ T cells are clonally shared with tissue-resident intraepithelial lymphocytes in celiac disease. Linn Eggesbø, Louise F. Risnes, Stephanie Zühlke, Shiva Dahal-Koirala, Ralf S. Neumann, Knut E. A. Lundin, Asbjørn Christophersen, Ludvig M. Sollid. Mucosal Immunol (2021). DOI: 10.1038/s41385-021-00385-8. The manuscript is included in the thesis. Also available at: https://doi.org/10.1038/s41385-021-00385-8 |