Fabri, Astrid;
(2025)
Characterisation of pancreas-infiltarting CD4+ T cells in type 1 diabetes.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterised by immune-mediated destruction of pancreatic β-cells, resulting in hyperglycaemia. While CD4+ T cells have been strongly implicated in T1D pathogenesis, the precise identity and phenotype of the cells infiltrating the pancreatic islets remains poorly defined. A detailed understanding of the CD4+ T cells present at the site of autoimmune attack would be helpful in designing approaches to inhibit T1D development. In this project, we employed spectral flow cytometry to comprehensively characterise pancreas-infiltrating CD4+ T cells in the DO11 x RIP-mOVA mouse model of T1D. We designed and optimised two 33-colour spectral flow cytometry panels, enabling high-dimensional immunophenotyping of these cells. Recognising the limitations of manual gating for such complex datasets, we developed a robust bioinformatics pipeline combining unbiased cell clustering, marker enrichment modelling, and algorithm-guided gating strategies for the identification and validation of novel T cell populations. Through this approach, we discovered a previously uncharacterized CD4+ T cell subset in the pancreas of DO11 x RIP-mOVA mice that resembles the T-resident helper (Trh) cells recently identified in the lung in the context of chronic viral infection. These cells exhibited features similar to T follicular helper (Tfh) cells, but were distinguished by their resistance to co-stimulation blockade and unique transcriptional and cytokine profiles. Importantly, re-analysis of publicly available single-cell RNA sequencing datasets revealed the presence of analogous Trh-like populations in the NOD mouse model of T1D, suggesting broader relevance of this work. The findings presented in this thesis provide further insight into the phenotype of pancreas-infiltrating CD4+ T cells in autoimmunity and may contribute to the development of novel and more targeted therapeutic strategies for individuals with T1D.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Characterisation of pancreas-infiltarting CD4+ T cells in type 1 diabetes |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10216547 |
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