Khan, Ayesha;
(2024)
Investigating the anti-microbial capabilities of gamma delta T cells.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Gamma delta T (γδT) cells represent a subset of T lymphocytes that exhibit a variety of functions, from killing capacity in response to stress ligands to the ability to kill bacteria such as Escherichia coli (E. coli) and behaviour similar to professional antigen-presenting cells (pAPCs) upon expansion, as shown previously by our group. As γδT cells are not restricted by the requirement of antigen to be presented on major histocompatibility complex (MHC) molecules, they display rapid pro-inflammatory reactions. We aimed to further investigate these responses by exploring the capacity of γδT cells to kill both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative E. coli bacteria by using an ex vivo co-culture model of isolated γδT cells and bacteria. We intended to elucidate the nature of this killing by comparing freshly-isolated and 14-day zoledronate-expanded γδT cells, to explore whether expansion via zoledronate impacts the bactericidal activity of γδT cells. Our results show that i) zoledronate-expanded γδT cells kill bacteria to the same degree as freshly-isolated γδT cells and that ii) freshly-isolated γδT cells can kill bacteria more significantly than other freshly-isolated immune cells and, through use of nalm-6 cells as comparators, iii) freshly-isolated γδT cells can innately kill bacteria more significantly compared to killing of cancer cells. Focussing further on freshly-isolated γδT cells, we then explored the cell markers and receptors involved in γδT cell-mediated killing of E. coli and S. aureus. Through use of blocking antibodies to the TLR-2, TLR-4 and CD14 receptors, as well as TAK-242; in combination with flow cytometric analysis of γδT cells, we have established that killing of bacteria by γδT cells utilizes innate signals and receptors. Further identification of the involvement of these receptors may enable the development of new classes of small and medium size molecules that can be used as alternative anti-microbials.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the anti-microbial capabilities of gamma delta T cells |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | 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 Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10198536 |
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