Schnurri-2 controls memory Th1 and Th2 cell numbers in vivo
Schnurri-2 controls memory Th1 and Th2 cell numbers in vivo
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DOI：
10.4049/jimmunol.178.8.4926
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发表时间：
2007-04-15
影响因子：
4.4
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Kimura, Motoko Y.;Iwamura, Chiaki;Nakayama, Toshinori
Schnurri - 2（Shn - 2）是一种含大量锌指结构的蛋白质，它在细胞生长、信号转导和淋巴细胞发育中起关键作用。在Shn - 2缺陷型CD4 T细胞中，NF - κB的激活上调，其分化为Th2细胞的能力增强。我们在此证明，从Shn - 2缺陷型效应Th1/Th2细胞不能正常产生Th1和Th2记忆细胞。甚至在将效应Th1/Th2细胞转移到同基因小鼠体内一周后，就检测到Shn - 2缺陷型供体T细胞数量显著减少，尤其是在淋巴器官中。转移的Shn - 2缺陷型Th1/Th2细胞表达更高水平的激活标志物CD69。在Shn - 2缺陷型转移的CD4 T细胞中，未观察到BrdU掺入有明显缺陷。Shn - 2缺陷型供体Th1/Th2细胞群中凋亡细胞数量选择性地更高。此外，Shn - 2缺陷型效应Th1和Th2细胞在体外培养中对细胞死亡的敏感性增加，FasL表达增加。转移过表达NF - κB的p65亚基的Th2效应细胞导致淋巴器官中p65表达细胞数量减少。正如预期的那样，Shn - 2缺陷型小鼠体内免疫后T细胞依赖性抗体应答显著降低。因此，Shn - 2似乎通过改变记忆Th1/Th2细胞对细胞死亡的敏感性来控制其产生。
Schnurri-2 (Shn-2) is a large zinc-finger containing protein, and it plays a critical role in cell growth, signal transduction and lymphocyte development. In Shn-2-deficient CD4 T cells, the activation of NF-kappa B was up-regulated and their ability to differentiate. into Th2 cells was enhanced. We herein demonstrate that Th1 and Th2 memory cells are not properly generated from Shn-2-deficient effector Th1/Th2 cells. Even a week after the transfer of effector Th1/Th2 cells into syngeneic mice, a dramatic decrease in the number of Shn-2-deficient donor T cells was detected particularly in the lymphoid organs. The transferred Shn-2-deficient Th1/Th2 cells express higher levels of the activation marker CD69. No significant defect in the BrdU incorporation in the Shn-2-deficient transferred CD4 T cells was observed. The numbers of apoptotic cells were selectively higher in Shn-2-deficient donor Th1/Th2 cell, population. Moreover, Shn-2-deficient effector Th1 and Th2 cells showed an increased susceptibility to cell death in in vitro cultures with increased expression of FasL. Transfer of Th2 effector cells over-expressing the p65 subunit of NF-kappa B resulted in a decreased number of p65-expressing cells in the lymphoid organs. As expected, T cell-dependent Ab responses after in vivo immunization of Shn-2-deficient mice were significantly reduced. Thus, Shn-2 appears to control the generation of memory Th1/Th2 cells through a change in their susceptibility to cell death.