Thompson, Emily2019-12-112019-12-112017-08https://hdl.handle.net/11299/209007University of Minnesota Ph.D. dissertation. August 2017. Major: Microbiology, Immunology and Cancer Biology. Advisor: Vaiva Vezys. 1 computer file (PDF); xii, 160 pages + 2 supplementary files.CD8+ T cells can recognize any infected cell of the body, making them essential in the immune response against intracellular pathogens. A critical function of CD8+ T cells is the directed killing of target cells through cytolysis. This mechanism is dependent on direct cell-cell contact, which makes the migratory capacity of CD8+ T cells paramount to their successful immune response. The small intestine (SI) is the biggest mucosal surface between the host and the environment. The immune system in this compartment must actively eliminate infection while maintaining tolerance to normal flora, self, and food-antigen. Using two-photon laser scanning microscopy, I evaluated foreign- and self-specific CD8+ T cell motility in the SI. I found that foreign-antigen specific CD8+ T cell behavior varied throughout infection, and was independent of the αE integrin. Interestingly, self-specific CD8+ T cells were initially reactive to self-antigen in vivo but this behavior was altered after further tolerance induction. These studies inform our understanding of the requirements for effective CD8+ T cell immunosurveillance in the SI. I also evaluated what characterizes and contributes to a self-specific CD8+ T cell response to protein in the SI. Using a heterologous prime-boost-boost (HPBB) approach, I generated functional self-specific CD8+ T cells. This response matured throughout boosting, showing the potential of self-specific CD8+ T cells. I also used HPBB to evaluate foreign-antigen specific CD8+ T memory development and showed that the time interval between each boost impacts CD8+ T cell memory longevity.enAutoimmunityCD8+ T cellsMigrationMotilityToleranceVaccineThesis or Dissertation