Dissertation
Modification of the Homing and Function of Regulatory T-cells for the Prevention of Acute Graft-Versus-Host Disease
University of the Sunshine Coast, Queensland
Doctor of Philosophy, University of the Sunshine Coast
2020
DOI:
https://doi.org/10.25907/00543
Abstract
Graft-Versus-Host Disease (GVHD) is a serious complication following hematopoietic stem cell transplantation (HSCT), that continues to be the leading cause of non-relapse morbidity and mortality in HSCT patients. Acute GVHD occurs in roughly 40% of HSCT recipients. It is the result of an unregulated expansion and activation of donor derived effector T-cells, which leads to a pro-inflammatory immune response and multi-organ damage and ultimately reduces the survival rates of HSCT recipients. Despite our growing understanding of acute GVHD, preventative treatment strategies continue to have limited success. One promising alternative approach is the use of a regulatory T-cell based cell therapies, which have sparked considerable interest as a potential therapeutic treatment for acute GVHD. Regulatory T-cells (Treg) are a subset of CD4+ T-cells that play an integral role in immune regulation and in maintaining self-tolerance. Treg have also been shown to be important in the development and prevention of acute GVHD. However, there are number of limitations that have significantly delayed the wider use of Treg-based cell therapies in the clinic, namely the high therapeutic dose required for effective disease suppression and the limited availability of Treg in vivo. Therefore, the scope of this thesis project focused on enhancing Treg-mediated acute GVHD suppression, by either augmenting Treg function or by modifying Treg 'homing' to directly target the cell therapy towards affected organ systems.
Details
- Title
- Modification of the Homing and Function of Regulatory T-cells for the Prevention of Acute Graft-Versus-Host Disease
- Authors
- Jemma Nicholls
- Contributors
- David J McMillan (Supervisor)
- Awarding institution
- University of the Sunshine Coast
- Degree awarded
- Doctor of Philosophy
- Publisher
- University of the Sunshine Coast, Queensland
- DOI
- 10.25907/00543
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99450984102621
- Output Type
- Dissertation
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