Regulations of Fas ligand (CD178) in Murine CD8+cytotoxic T lymphocyte Populations
Martin, James Sean, Department of Microbiology, University of Virginia
Braciale, Tom, Department of Microbiology, University of Virginia
Bender, Tim, Department of Microbiology, University of Virginia
Ravichandran, Kodi, Department of Microbiology, University of Virginia
Hahn, Young, Department of Microbiology, University of Virginia
Duling, Brian, Department of Biomedical Engineering, University of Virginia
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.
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PHD (Doctor of Philosophy)
English
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2008/01/01