The regulatory effects of CD161 and MAIT cells

Mucosal associated invariant T (MAIT) cells are connected with the potential regulation of anti-tumour responses, although their role in this regulation is poorly defined. In cancer, the relative frequency of MAIT cells has an impact on patient outcome, although how this impact is mediated is not known. Therefore, we have carefully modulated the frequency of MAIT cells within cultures and assessed the effect this has on the anti-tumour functions of important immune cells such as NK and conventional T cells. We identified that changes in MAIT cell frequency can significantly impact the ability of NK cells to become activated and produce proinflammatory cytokines. Interestingly, changes in MAIT cell frequency do not impact conventional T cell activation, but can alter pro-inflammatory cytokine expression. We also identified trends that suggest alterations in MAIT cell frequency may suppress a broad range of cytokines produced within the PBMC pool. The thesis also examined the potential regulatory impact of the cell surface molecule CD161 on T cells (particularly MAIT cells). Several distinctive characteristics have been identified that provides a broader understanding of the effect ligating and blocking this molecule can have. We have demonstrated that interaction with CD161 can promote activation and affect cytokine and perforin expression by MAIT cells. Conventional T cells are also affected, specifically their cytokine expression and activation. Lastly, we also performed several pilot studies, which identified changes in the expression of some genes of interest (e.g. IL-13, IL-5) and raised the possibility that the products of these genes could also be affected. Taken together, our research indicates that MAIT cell frequency can have significant effects on the anti-tumour roles of other immune cells. Additionally, we have furthered the understanding of which anti-tumour functions CD161 interaction can affect. CD161 has the potential to be used as an immunotherapeutic target in cancer patients, but more knowledge is required to determine the host of potential functions CD161 may affect. We suggest that further study is required, particularly in determining the effect CD161 ligation and blocking can have on cytokine output on a range of cells, including MAIT cells.%%%%Doctor of Philosophy