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Regulations of Fas Ligand (CD178) in Murine CD8+Cytotoxic T Lymphocyte Populations

Martin, James Sean
Thesis/Dissertation; Online
Martin, James Sean
Duling, Brian
Braciale, Tom
Bender, Tim
Ravichandran, Kodi
Hahn, Young
CD8+ cytotoxic T lymphocytes(CTL) are important for controlling a myriad of infectious agents in humans and mice CD8+ CTL utilize a variety of cytotoxic mechanisms to kill infected cells. The most well known cytotoxic mechanism used by CD8+ T cells revolves around the release of cytotoxic molecules perforin and granzymes from preformed granules within the CD8+ T cell. Fas ligand(CD178) is a 40kDa membrane bound protein that can be expressed by CD8+ T cells after activation and can cause death of target cells bearing the Fas(CD95) receptor. Investigators have documented the expression of fas ligand in intracellular stores in CD4+ T cells, NK cells, and CD8+ T cells. However, a recent report has contradicted the previous reports documenting fas ligand expression in intracellular stores. We examined the expression of intracellular fas ligand in effector CD8+ T cells in order to resolve the question of whether fas ligand was expressed in intracellular stores in CD8+ T cells. We hypothesized that primary effector CD8+ T cells would not expression functional stores of intracellular fas ligand, while long term CD8+ T cell clones and lines would express a functional store of fas ligand. Our results indicate that primary effector CD8+ T cells derived either from in vitro culture or in vivo during acute infection do not express a detectable store of intracellular fas ligand. In contrast, a CD8+ T cell clone and a long term T cell line did express a functional store of intracellular fas ligand. These results suggest that long term exposure to antigen and differentiation cytokines such as IL-2 may induce further differentiation of primary effector CD8+ T cells into a discrete subset of CD8+ T cells that express an intracellular store of fas ligand. Note: Abstract extracted from PDF text
University of Virginia, Department of Microbiology, PHD (Doctor of Philosophy), 2008
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PHD (Doctor of Philosophy)
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