Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1
Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1
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DOI：
10.1189/jlb.0809575
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发表时间：
2010-06-01
影响因子：
5.5
通讯作者：
Alexander-Miller, Martha A.
中科院分区：
文献类型：
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作者：
Arimilli, Subhashini;Sharma, Sharad K.;Alexander-Miller, Martha A.
CD 8（+）T细胞在呼吸道病原体的清除中起关键作用。因此，令人惊讶的是，在许多病毒感染模型中观察到肺效应物的功能失活。目前，导致这些细胞功能关闭的分子缺陷尚不清楚。在本研究中，我们解决了这个问题，使用副粘病毒SV 5的呼吸道感染模型。发现无功能细胞表现出SOCE降低，导致NFAT 1活化降低。值得注意的是，功能可以通过提供增加的细胞外钙水平来恢复。动员钙的能力降低与CRAC通道亚基ORAI 1的表达降低有关。这些发现揭示了效应T细胞功能负调节的一种以前未知的机制。J. Leukoc. 87：977-988; 2010.
CD8(+) T cells play a critical role in the clearance of respiratory pathogens. Thus, it is surprising that functional inactivation of lung effectors has been observed in many models of viral infection. Currently, the molecular defect responsible for the shut-off of function in these cells is unknown. In the present study, we addressed this question using a model of respiratory infection with the paramyxovirus SV5. Nonfunctional cells were found to exhibit decreases in SOCE, resulting in reduced NFAT1 activation. Notably, function could be restored by the provision of increased levels of extracellular calcium. The reduced ability to mobilize calcium was associated with reduced expression of ORAI1, the CRAC channel subunit. These findings reveal a previously unknown mechanism for the negative regulation of function in effector T cells. J. Leukoc. Biol. 87: 977-988; 2010.