Doctor of Philosophy
Microbiology and Immunology
Severe cases of influenza A virus (IAV) infection are often complicated by concomitant bacterial pneumonia or sepsis. Many bacterial species are capable of producing potent immunomodulators called superantigens (SAgs), which have the potential to interfere with cell-based antiviral immune mechanisms. I asked what effects bacterial SAgs have on both the magnitude and the breadth of antiviral CD8+ T cell (TCD8+) responses. Surprisingly, administration of SAgs to mice shortly before or after vaccination with IAV increased the number of primary TCD8+ responding to select IAV-derived epitopes. T cell receptor staining of these SAg-augmented populations revealed expression of Vβ regions that bind SAgs. In vivo evaluation of the cytotoxic capability of these cells revealed increased killing of target cells pulsed with viral peptides. Memory TCD8+ specific for IAV were also expanded by certain SAgs and displayed increased effector functions, though the effect of SAgs on TCD8+ recall depended critically on the timing of SAg injection relative to priming and boosting inoculation of IAV. Though SAg exposure did not augment local pulmonary TCD8+ responses to active IAV infection, it also did not impair these responses as measured by the effect on weight loss and viral titre. Finally, I show that SAg-induced augmentation of the magnitude, breadth and function of IAV-specific memory TCD8+ can be recapitulated in in vitro experiments utilizing human cells. This work elucidates an unexpected role for bacterial SAgs as potential enhancers of antiviral immunity in the context of TCD8+-based vaccination strategies.
Meilleur, Courtney, "Effect of Bacterial Superantigens on the Magnitude and Breadth of Influenza-Specific CD8+ T Cell Responses" (2018). Electronic Thesis and Dissertation Repository. 5874.
Available for download on Monday, December 14, 2020