Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Biol Chem. 2010 Nov 12;285(46):35393-405. doi: 10.1074/jbc.M110.145052. Epub 2010 Sep 13.
LAT (linker for activation of T cells) is a transmembrane adaptor protein that plays an essential role in TCR-mediated signaling and thymocyte development. Because LAT-deficient mice have an early block in thymocyte development, we utilized an inducible system to delete LAT in primary T cells to study LAT function in T cell activation, homeostasis, and survival. Deletion of LAT caused primary T cells to become unresponsive to stimulation from the TCR and impaired T cell homeostatic proliferation and long term survival. Furthermore, deletion of LAT led to reduced expression of Foxp3, CTLA-4, and CD25 in T(reg) cells and impaired their function. Consequently, mice with LAT deleted developed a lymphoproliferative syndrome similar to that in LATY136F mice, although less severe. Our data implicate that LAT has positive and negative roles in the regulation of mature T cells.
LAT（T 细胞激活连接蛋白）是一种跨膜衔接蛋白，在 TCR 介导的信号转导和胸腺细胞发育中发挥重要作用。由于 LAT 缺陷型小鼠的胸腺细胞发育早期受阻，我们利用诱导型系统在原代 T 细胞中删除 LAT，以研究 LAT 在 T 细胞激活、稳态和存活中的功能。LAT 的缺失导致原代 T 细胞对 TCR 的刺激无反应，并损害 T 细胞的稳态增殖和长期存活。此外，LAT 的缺失导致 Treg 细胞中 Foxp3、CTLA-4 和 CD25 的表达减少，并损害其功能。因此，LAT 缺失的小鼠表现出类似于 LATY136F 小鼠的淋巴增殖综合征，尽管程度较轻。我们的数据表明，LAT 在调节成熟 T 细胞方面具有正反两方面的作用。
