Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids
Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids
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DOI：
10.1126/sciimmunol.aaj1996
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发表时间：
2017-03-01
影响因子：
24.8
通讯作者：
Cockburn, I. A.
中科院分区：
文献类型：
--
作者：
McNamara, H. A.;Cai, Y.;Cockburn, I. A.
驻留在肝脏的CD8(+)T细胞是高度活跃的细胞，它巡逻在血管系统中，提供对肝脏病原体的保护。一个关键的问题是：这些肝脏CD8(+)T细胞如何同时存在于循环和组织中？由于驻留在肝脏的T细胞不表达CD103，CD103是T细胞滞留在上皮组织中的关键整合素，因此我们研究了其他候选黏附分子。利用活体显像，我们发现CD8(+)T细胞在肝窦中的巡视依赖于LFA-1-ICAM-1(细胞间黏附分子-1)的相互作用。与效应记忆细胞相比，驻留在肝脏的CD8(+)T细胞上调LFA-1，可能是为了促进这一行为。最后，我们发现，在疟原虫免疫或淋巴细胞性脉络膜脑膜炎病毒感染后，LFA-1缺陷的CD8(+)T细胞未能形成实质性的驻肝记忆群体。总而言之，我们的结果表明，正是通过LFA-1的黏附，才允许驻留在肝脏的记忆CD8(+)T细胞巡逻并停留在肝窦中。
Liver-resident CD8(+) T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: How can these liver CD8(+) T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD 103-a key integrin for T cell residence in epithelial tissues-we investigated other candidate adhesion molecules. Using intravital imaging, we found that CD8(+) T cell patrolling in the hepatic sinusoids is dependent on LFA-1-ICAM-1 (intercellular adhesion molecule-1) interactions. Liver-resident CD8(+) T cells up-regulate LFA-1 compared with effector memory cells, presumably to facilitate this behavior. Last, we found that LFA-1-deficient CD8(+) T cells failed to form substantial liver-resident memory populations after Plasmodium immunization or lymphocytic choriomeningitis virus infection. Collectively, our results demonstrate that it is adhesion through LFA-1 that allows liver-resident memory CD8(+) T cells to patrol and remain in the hepatic sinusoids.