Requirements for selection of conventional and innate T lymphocyte lineages
Requirements for selection of conventional and innate T lymphocyte lineages
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DOI：
10.1016/j.immuni.2007.09.012
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发表时间：
2007-11-01
期刊：
影响因子：
32.4
通讯作者：
Schwartzberg, Pamela L.
中科院分区：
文献类型：
--
作者：
Horai, Reiko;Mueller, Kristen L.;Schwartzberg, Pamela L.
缺乏Tec激酶Itk的小鼠会产生大量CD8(+) T细胞，这些细胞具有一些特性，包括记忆标记的表达、细胞因子的快速产生和对白细胞介素-15的依赖，类似于NKT和其他先天T细胞谱系。与NKT细胞一样，这些CD8(+) T细胞可以在造血细胞上被选择。我们证明，这些CD8(+) T细胞的表型是由造血细胞的选择导致的——胸腺基质上的强制选择减少了成熟的ltk缺陷CD8(+) T细胞的数量和先天表型。我们进一步表明，与NKT细胞类似，Itk（-/-）小鼠中先天型CD8(+) T细胞的选择需要适配体SAP。然而，其先天特征的获得需要CD28。我们的研究结果表明，SAP和Itk分别相互调节先天和常规CD8(+) T细胞在造血细胞和胸腺上皮上的选择，而CD28调节先天表型的发育，这是由造血细胞的选择引起的。
Mice deficient in the Tec kinase Itk develop a large population of CD8(+) T cells with properties, including expression of memory markers, rapid production of cytokines, and dependence on Interleukin-15, resembling NKT and other innate T cell lineages. Like NKT cells, these CD8(+) T cells can be selected on hematopoietic cells' We demonstrate that these CD8(+) T cell phenotypes resulted from selection on hematopoietic cells-forcing selection on the thymic stroma reduced the number and innate phenotypes of mature ltk-deficient CD8(+) T cells. We further show that, similar to NKT cells, selection of innate-type CD8(+) T cells in Itk(-/-) mice required the adaptor SAP. Acquisition of their innate characteristics, however, required CD28. Our results suggest that SAP and Itk reciprocally regulate selection of innate and conventional CD8(+) T cells on hematopoietic cells and thymic epithelium, respectively, whereas CD28 regulates development of innate phenotypes resulting from selection on hematopoietic cells.