Temporal differences in the dependency on Phosphoinositide dependent kinase 1 distinguish the development of Vα14 iNKT cells, regulatory T cells and conventional T cells
Citation:
Finlay DK, Kelly AP, Clarke R, Sinclair LV, Deak M, Alessi DR, Cantrell DA, Temporal differences in the dependency on Phosphoinositide dependent kinase 1 distinguish the development of Vα14 iNKT cells, regulatory T cells and conventional T cells, Journal of Immunology, 185, 10, 2010, 5973 - 5982Download Item:
Abstract:
The present 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?14 NKT cells but can differentiate to conventional CD4, CD8 or regulatory T cell subsets in the thymus. The PDK1 requirement for V?14 NKT cell development reflects that these cells require the PDK1 substrate Protein Kinase B (PKB, also called Akt) to meet the metabolic demands for proliferative expansion in response to Interleukin 15 or antigen receptor stimulation. There is also constitutive PDK1 signaling in conventional ?/? T cells that is not required for lineage commitment of these cells but fine-tunes the expression of coreceptors and adhesion molecules. Also, while PDK1 is dispensable for thymic development of conventional ?/? T cells, peripheral cells are substantially reduced. 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.
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http://people.tcd.ie/finlaydDescription:
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Author: Finlay, David
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Journal ArticleCollections
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Journal of Immunology185
10
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Immunology, T cellsSubject (TCD):
Immunology, Inflammation & InfectionMetadata
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