Master of Science
Microbiology and Immunology
Mucosa-associated invariant T (MAIT) cells are innate-like T cells that are activated by microbial vitamin B metabolites and/or cytokine stimulation to produce pro-inflammatory cytokines and cytotoxic granules. Influenza A viruses (IAVs) activate MAIT cells in a by-stander manner, and their abundance negatively correlates with infection-induced morbidity and mortality. However, how MAIT cells directly contribute to anti-viral immunity is ill-defined. I hypothesized that MAIT cells’ presence in mice enhances antigen-specific CD8+ T cell responses. I observed a trend that MAIT cell-deficient mice generally developed smaller populations of antigen-specific CD8+ T cells following IAV exposure than mice abundant in MAIT cells, with this difference being pronounced amongst female mice. Co-administration of IAV and a potent MAIT cell ligand did not influence the anti-IAV CD8+ T cell response, but induced rapid MAIT cell accumulation in the peritoneal cavity. These results indicate that MAIT cells are poised to influence anti-viral adaptive immune responses.
Summary for Lay Audience
Influenza A viruses are a major source of morbidity and mortality worldwide, with annual infections keeping working people away from their jobs, sending others to the hospital, and ultimately killing thousands. Influenza A viruses change very quickly, which often allows them to be unaffected by anti-viral medications, and also requires us to get new vaccines every year. Our ability to prevent and treat influenza A viral infections is clearly poor and needs improvement. My research evaluated how two different immune cells, CD8+ T cells and mucosa-associated invariant T (MAIT) cells, work together to combat influenza A viruses. CD8+ T cells are able to specifically detect and kill influenza-infected cells, and can be re-activated to fight future influenza infections. Influenza can activate MAIT cells to release signals that have the potential to increase the virus-killing capacity of CD8+ T cells. I found that mice that have many MAIT cells tended to have CD8+ T cells with enhanced potential to kill influenza when compared to mice that lacked MAIT cells. These findings indicate that targeting MAIT cells with anti-viral medications and vaccines may promote the development of a killer CD8+ T cell response that is capable of treating and preventing dangerous influenza A viral infections.
Wardell, Christine Marie, "Mucosa-Associated Invariant T Cell Roles And Local Responses In Cell-Mediated Immunity To Influenza A Virus" (2019). Electronic Thesis and Dissertation Repository. 6318.
Available for download on Thursday, July 01, 2021