Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Immunity. 2010 Aug 27;33(2):203-15. doi: 10.1016/j.immuni.2010.07.013. Epub 2010 Jul 30.
CD8(+) T cells are selected via low-affinity interaction with MHC class I molecules on thymic epithelial cells (TECs). However, compromised T cell receptor signaling was proposed to force CD8(+) T cell selection on hematopoietic cells through a SLAM-associated protein (SAP)-dependent mechanism similar to NKT cells. The outcome is an unconventional CD8(+) T cell with phenotypic and functional characteristics of innate lymphocytes. Here we showed that Id3(-/-) CD8(+) T cells had an innate-like phenotype and required SAP for their development. However, like conventional CD8(+) T cells, Id3(-/-) CD8(+) thymocytes were selected on TECs. The requirement for SAP and the innate-like phenotype was not intrinsic to Id3(-/-) CD8(+) thymocytes. Rather, an expanded population of NKT-like cells induced the innate phenotype on CD8(+) T cells through production of interleukin-4. Our findings reveal that accumulation of NKT-like cells promotes conventional CD8(+) thymocytes to acquire innate lymphocyte characteristics.
CD8(+) T 细胞通过与胸腺上皮细胞 (TEC) 上 MHC Ⅰ类分子的低亲和力相互作用被选择。然而，据报道，T 细胞受体信号受损会通过类似于 NKT 细胞的 SLAM 相关蛋白 (SAP) 依赖性机制迫使造血细胞上的 CD8(+) T 细胞选择。其结果是一种非常规的 CD8(+) T 细胞，具有先天淋巴细胞的表型和功能特征。在这里，我们表明 Id3(-/-) CD8(+) T 细胞具有先天样表型，并且其发育需要 SAP。然而，与常规 CD8(+) T 细胞一样，Id3(-/-) CD8(+)胸腺细胞在 TEC 上被选择。SAP 和先天样表型的需求不是 Id3(-/-) CD8(+)胸腺细胞所固有。相反，通过产生白细胞介素-4，大量的 NKT 样细胞诱导 CD8(+) T 细胞获得先天淋巴细胞特征。我们的研究结果表明，NKT 样细胞的积累促进了常规 CD8(+)胸腺细胞获得先天淋巴细胞特征。
