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    β-catenin, TCF, and ICAT in T cell development, function, and aging

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    Author
    Hossain, Mohammad
    Advisor
    Sen, Jyoti, 1953-
    Livak, Ferenc
    Date
    2009
    Type
    dissertation
    
    Metadata
    Show full item record
    Other Titles
    Beta-Catenin, TCF, and ICAT in T Cell Development, Function, and Aging
    Abstract
    Both T cell factor (TCF) and beta-catenin play important roles during different stages of T cell development. Most strikingly, deletion of TCF results in a block early in development, which becomes complete with TCF-LEF double deletion. Similarly, T-cell specific deletion of beta-catenin impairs T cell development at the beta-selection checkpoint. However, in addition to working together to drive expression of beta-catenin-TCF target genes, both TCF and beta-catenin have the potential to work independently of each other. To specifically study the role of beta-catenin-TCF interactions during T cell development, function, and aging, we generated transgenic mice that express ICAT (Inhibitor of beta-Catenin and TCF), a naturally occurring inhibitor of beta-catenin-TCF interactions, in the T cell lineage. We found that disruption of beta-catenin-TCF interactions by ICAT expression impairs survival of thymocytes without significantly affecting their differentiation or proliferation. Interestingly, thymocyte aging shows signs of slowing down in ICAT-Tg mice, implicating beta-catenin-TCF interactions in normal thymic involution. We further show that beta-catenin-TCF interactions provide survival signals to activated T cells and promote differentiation of activated CD4 T cells into the default Th2 lineage. However, TCF represses Th1 differentiation independently of its interaction with beta-catenin. Finally, we show that beta-catenin expression accelerates the onset of aging in mature T cells. Collectively, these findings provide novel insights into the function of TCF and beta-catenin in T cell development, function, and aging.
    Description
    University of Maryland, Baltimore. Molecular Medicine. Ph.D. 2009
    Keyword
    ICAT
    TCF
    Th2 differentiation
    thymic involution
    Apoptosis
    beta Catenin
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/893
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    Theses and Dissertations School of Medicine
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