Temporal differences in the dependency on phosphoinositide-dependent kinase 1 distinguish the development of invariant V alpha 14 NKT cells and conventional T cells

David K. Finlay, April P. Kelly, Rosemary Clarke, Linda V. Sinclair, Maria Deak, Dario R. Alessi, Doreen A. Cantrell

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    20 Citations (Scopus)

    Abstract

    This study uses two independent genetic strategies to explore the requirement for phosphoinositide-dependent kinase-1 (PDK1) in the development of mature T cell populations from CD4/CD8 double-positive thymocytes. The data show that CD4/CD8 double-positive thymocytes that do not express PDK1 or express a catalytically inactive PDK1 mutant fail to produce mature invariant V alpha 14 NKT cells but can differentiate to conventional CD4, CD8, or regulatory T cell subsets in the thymus. The PDK1 requirement for V alpha 14 NKT cell development reflects that these cells require the PDK1 substrate protein kinase B to meet the metabolic demands for proliferative expansion in response to IL-15 or AgR stimulation. There is also constitutive PDK1 signaling in conventional alpha/beta T cells that is not required for lineage commitment of these cells but fine-tunes the expression of coreceptors and adhesion molecules. Also, although PDK1 is dispensable for thymic development of conventional alpha/beta T cells, peripheral cells are reduced substantially. This reflects a PDK1 requirement for lymphopenia-induced proliferation, a process necessary for initial population of the peripheral T cell niche in neonatal mice. PDK1 is thus indispensable for T cell developmental programs, but the timing of the PDK1 requirement is unique to different T cell subpopulations. The Journal of Immunology, 2010, 185: 5973-5982.

    Original languageEnglish
    Pages (from-to)5973-5982
    Number of pages10
    JournalJournal of Immunology
    Volume185
    Issue number10
    Early online date13 Oct 2010
    DOIs
    Publication statusPublished - 15 Nov 2010

    Keywords

    • NF-Kappa-B
    • Deficient mice
    • C-MYC
    • PDK1
    • Lineage
    • AKT
    • Activation
    • Expression
    • Receptor
    • Differentiation

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