Temporal Differences in the Dependency on Phosphoinositide-Dependent Kinase 1 Distinguish the Development of Invariant Vα14 NKT Cells and Conventional T Cells
Temporal Differences in the Dependency on Phosphoinositide-Dependent Kinase 1 Distinguish the Development of Invariant Vα14 NKT Cells and Conventional T Cells
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DOI：
10.4049/jimmunol.1000827
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发表时间：
2010-11-15
影响因子：
4.4
通讯作者：
Cantrell, Doreen A.
中科院分区：
文献类型：
--
作者：
Finlay, David K.;Kelly, April P.;Cantrell, Doreen A.
这项研究使用两种独立的遗传策略来探索从CD4/CD8双阳性胸腺细胞发育成成熟的T细胞群体中对磷酸肌醇依赖的激酶-1(PDK1)的需求。数据显示，不表达PDK1或表达催化失活的PDK1突变体的CD4/CD8双阳性胸腺细胞不能产生成熟的不变Vα14 NKT细胞，但可以分化为胸腺中传统的CD4、CD8或调节性T细胞亚群。Vα14 NKT细胞发育所需的PDK1反映了这些细胞需要PDK1底物蛋白激酶B来满足对IL-15或AGR刺激而进行增殖扩张的代谢需求。在传统的α/βT细胞中也存在结构性的PDK1信号，这不是这些细胞的谱系承诺所必需的，但可以微调辅助受体和黏附分子的表达。此外，虽然PDK1对于传统的α/βT细胞的胸腺发育是必不可少的，但外周细胞显著减少。这反映了PDK1对淋巴细胞减少诱导的增殖的要求，这是新生小鼠外周T细胞生态位初始种群所必需的过程。因此，PDK1对于T细胞发育程序是必不可少的，但不同的T细胞亚群需要PDK1的时间是唯一的。《免疫学杂志》，2010,185：5973-5982。
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.