T cell factor-1 regulates CD4+ and CD8+ T cell responses in a stage-specific manner T CELL FACTOR-1 REGULATES CD4 + AND CD8 + T CELL RESPONSES IN A STAGE-SPECIFIC MANNER

Jodi Gullicksrud, Jodi Gullicksrud, Hai-Hui Xue, Vladimir, John, John Colgan, Steven Harty, Varga
2017 unpublished
PUBLIC ABSTRACT In order to mount an effective defense against a wide variety of potential infections, an immune response will coordinate multiple arms of the immune system, thus providing a multifaceted attack against the infective agent. Upon infection with a virus, the immune system will mount 2 types of responses: (1) a humoral immune response that is made up of responding B cells, which produce antibodies against the specific virus, and (2) a cellular immune response, which consists
more » ... nantly of responding T cells that are also specific to the virus. T cells are either CD4 + T cells or CD8 + T cells. CD8 + T cells produce molecules to kill infected cells and clear the infection. CD4 + T cells provide help to other responding cells, such as B cells, to enhance the overall immune response. After the infection is cleared, a subset of CD4 + and CD8 + T cells persist to form memory T cells. Memory T cells are maintained for long periods of time, often the lifetime of the host, and provide a faster and stronger response upon re-infection with the same virus. Before they become activated during infection, both CD4 + and CD8 + T cells express high levels of a protein called T cell factor-1 (TCF1). TCF1 is important in the long-term persistence of memory CD8 + T cells after viral infection. In this dissertation, I demonstrated that TCF1 is also important for the generation of CD4 + T cells that provide help to responding B cells, which promotes effective antibody responses. Furthermore, similar to CD8 + T cells, TCF1 is also critical in the transition to memory CD4 + T cells after viral clearance. Therefore, TCF1 has crucial roles in the function of CD4 + T cells during viral infection, as well as the maintenance of the responding CD4 + and CD8 + T cells after the infection has been cleared. This places TCF1 as a useful target for optimizing T cell responses to both viral infections and potential vaccination strategies. ix