Regulation of CD8 T cell memory by ADAP
2014-12
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Regulation of CD8 T cell memory by ADAP
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2014-12
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During acute infections, naïve antigen-specific CD8 T cells are activated and differentiate into effector T cells, the majority of which undergo contraction after pathogen clearance. A small population of CD8 T cells survives the contraction phase and persists as memory, to protect against future infections. Memory CD8 T cells are heterogeneous and can be found in secondary lymphoid organs (SLOs), blood and non-lymphoid tissues (NLTs). Here I demonstrate the adaptor protein ADAP enhances the formation of memory CD8 T cells in both SLOs and NLTs after pathogen challenge. ADAP-deficient memory CD8 T cells in SLOs proliferate robustly to a systemic secondary challenge. Additionally, ADAP-deficient resident memory CD8 T cells are functional in response to local peptide challenge, but only when in the presence of wild-type antigen-specific T cells. In the absence of an infection, memory-like or memory phenotype (MP) CD8 T cells can arise from homeostatic cytokine exposure during lymphopenia. In contrast to the role of ADAP after pathogen challenge, I have identified a negative regulatory role for ADAP in the formation of MP CD8 T cells in the steady state. Naïve ADAP-deficient CD8 T cells are hyperresponsive to lymphopenia in vivo and exhibit enhanced activation of STAT5 and homeostatic antigen-independent proliferation in vitro in response to IL-15. My results indicate that ADAP dampens naïve CD8 T cell responses to lymphopenia and IL-15, and demonstrates a novel antigen-independent function for ADAP in the suppression of MP CD8 T cell generation. These findings contribute to our knowledge of the generation of different memory CD8 T cell populations, and we hope to augment vaccine efficacy and better understand the formation and maintenance of memory CD8 T cells.
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University of Minnesota Ph.D. dissertation. December 2014. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisor: Yoji Shimizu. 1 computer file (PDF); vii, 103.
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Fiege, Jessica. (2014). Regulation of CD8 T cell memory by ADAP. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/174850.
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