MEK kinase 1 is a negative regulator of virus-specific CD8+ T cells
MEK kinase 1 is a negative regulator of virus-specific CD8+ T cells
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DOI：
10.1002/eji.200535163
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Odum, Niels
中科院分区：
文献类型：
--
作者：
Labuda, Tord;Christensen, Jan Pravsgaard;Odum, Niels
MEK激酶1（MEKK1）是一种有效的JNK激活激酶，是体外T辅助细胞分化、细胞因子产生和增殖的调节剂。使用小鼠缺乏MEKK1活性（Mekk1（Delta KD））专门在他们的造血系统中，我们表明，MEKK1在病毒特异性免疫反应的产生中具有负调节作用。用水泡性口炎病毒（VSV）攻击的Mekk1（Delta KD）小鼠显示脾脏CD8（+）T细胞数量增加了4倍。相比之下，感染WT小鼠的脾T细胞数量仅略微增加。VSV感染后Mekk1（Delta KD）小鼠中的CD8（+）T细胞扩增具有病毒特异性，并且与WT动物相比，Mekk1（Delta KD）中病毒特异性T细胞的频率显著更高（超过3倍）。此外，在VSV感染后Mekk1（Delta KD）小鼠中观察到的T细胞过度扩增是增殖增加的结果，因为与病毒特异性WT CD8（+）T细胞相比，掺入BrdU的病毒特异性Mekk1（Delta KD）CD8（+）T细胞的百分比显著更高。相反，在VSV感染后，在Mekk1（Delta KD）和WT T细胞中检测到相似水平的凋亡。这些结果有力地表明，MEKK 1在体内病毒特异性CD8（+）T细胞的扩增中起负调节作用。
MEK kinase 1 (MEKK1) is a potent JNK-activating kinase, a regulator of T helper cell differentiation, cytokine production and proliferation in vitro. Using mice deficient for MEKK1 activity (Mekk1(Delta KD)) exclusively in their hematopoietic system, we show that MEKK1 has a negative regulatory role in the generation of a virus-specific immune response. Mekk1(Delta KD) mice challenged with vesicular stomatitis virus (VSV) showed a fourfold increase in splenic CD8(+) T cell numbers. In contrast, the number of splenic T cells in infected WT mice was only marginally increased. The CD8(+) T cell expansion in Mekk1(Delta KD) mice following VSV infection is virus-specific and the frequency of virus-specific T cells is significantly higher (more than threefold) in Mekk1(Delta KD) as compared to WT animals. Moreover, the hyper-expansion of T cells seen in Mekk1(Delta KD) mice after VSV infection is a result of increased proliferation, since a significantly higher percentage of virus-specific Mekk1(Delta KD) CD8(+) T cells incorporated BrdU as compared to virus-specific WT CD8(+) T cells. In contrast, similar levels of apoptosis were detected in Mekk1(Delta KD) and WT T cells following VSV infection. These results strongly suggest that MEKK1 plays a negative regulatory role in the expansion of virus-specific CD8(+) T cells in vivo.