Thesis
T cell gene therapy in vascular pathology
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2012
- Thesis identifier
- T13387
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- The immune system is a key contributor to atherosclerosis-related cardiovascular diseases (CVD) however, at present there are no targeted therapies specific for the inflamed vessel wall. Multiple leukocyte subsets have been shown to play a significant role in CVD and among them, CD4 T cells are receiving growing interest. Here we investigated whether T cells could be utilised as delivery vehicles in experimental atherosclerosis, for therapeutic molecules inserted via viral vector. Using multiphoton microscopy, we developed a protocol for the imaging of immune cells within the atherosclerotic aorta, confirming homing of a relevant number of leukocytes to the inflamed vessel following adoptive transfer. Transferred cells in the aorta were found to behave in a similar manner to cells found in the peripheral lymph nodes. We then constructed GFP and IL-10 expressing adenoviral vectors and used them in the optimisation of CD4+ T cell transduction. The biological activity of the produced IL-10 was assessed and GFP transduced cells were transferred into recipient mice and their migration tracked using flow cytometry. Transduction of CD4+ T cells reached 80%. IL-10 produced by the transduced cells was shown to be biologically active and importantly, the transferred modified cells were shown to migrate and survive comparably to non-transduced cells in a non-inflamed context without causing liver toxicity. Unfortunately, transduction of B6 T cells through various means was found to be unsuccessful therefore we could not evaluate the effect of IL-10 secreting T cells in atherosclerotic mice. In conclusion, the results of this thesis indicate that the use of genetically modified T cells could be a viable approach in the treatment of inflammatory disorders.
- Resource Type
- Note
- This thesis was previously held under moratorium from 16th May 2013 until 16th May 2017.
- DOI
- Date Created
- 2012
- Former identifier
- 999892313402996
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PDF of thesis T13387 | 2021-07-02 | Öffentlich | Herunterladen |