Trauma induces expansion and activation of a memory-like Treg population.
Trauma induces expansion and activation of a memory-like Treg population.
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创伤会引起类似记忆的Treg种群的扩张和激活。
DOI：
10.1002/jlb.4a0520-122r
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发表时间：
2021-03
影响因子：
5.5
通讯作者：
Lederer, James A.
中科院分区：
文献类型：
--
作者：
Yamakawa, Kazuma;Tajima, Goro;Keegan, Joshua W.;Nakahori, Yasutaka;Guo, Fei;Seshadri, Anupamaa J.;Cahill, Laura A.;Lederer, James A.
CD 4+调节性T细胞（TCRs）在创伤性损伤中被急性激活，这表明它们可能以与记忆性T细胞相似的动力学对损伤作出反应。在这里，我们使用小鼠烧伤创伤模型，通过将假手术或烧伤CD 45.1小鼠的T细胞转移到CD 45.2小鼠中并在受体小鼠中进行二次损伤来筛选记忆样T细胞对损伤的反应。在测量的所有T细胞亚群中，只有TcB在继发性损伤时扩增。扩增的T细胞是CD 44高/CD 62低亚群，其是记忆T细胞的标志物。使用CyTOF（飞行时间流式细胞术）质谱细胞术来证明损伤扩增的Tcells比来自未损伤小鼠的Tcells表达更高水平的CD 44、CTLA-4、ICOS、GITR和Helios。接下来，我们测试了类似的Tibetans种群是否会对烧伤创伤产生急性反应。我们观察到具有与损伤扩展的Tcls相匹配的表型的Tcls在损伤后6小时被激活。为了测试创伤导致的Treg激活是否需要功能性MHC II类，我们在MHC II类基因缺陷（MHC II-/-）小鼠或给予抗MHC II类抗体Fab片段以阻断TCR激活的小鼠中测量了创伤诱导的Treg激活。损伤诱导的Treg激活发生在正常小鼠中，但在MHCII−/−小鼠或给予Fab抗MHCII抗体的小鼠中仅检测到部分激活。这些发现表明，创伤激活记忆样Treg亚群，并且通过损伤激活Treg部分依赖于通过MHC II类依赖性机制的TCR信号传导。
CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, which suggests that they may react to injury with similar kinetics as memory T cells. Here, we used a mouse burn trauma model to screen for memory-like T cell responses to injury by transferring T cells from sham or burn CD45.1 mice into CD45.2 mice and performing secondary injuries in recipient mice. Among all T cell subsets that were measured, only Tregs expanded in response to secondary injury. The expanded Tregs were a CD44high/CD62Llow subpopulation, markers indicative of memory T cells. CyTOF (cytometry by time-of-flight) mass cytometry was used to demonstrate that injury-expanded Tregs expressed higher levels of CD44, CTLA-4, ICOS, GITR, and Helios than Tregs from noninjured mice. Next, we tested whether a similar population of Tregs might react acutely to burn trauma. We observed that Tregs with a phenotype that matched the injury-expanded Tregs were activated by 6 h after injury. To test if Treg activation by trauma requires functional MHC class II, we measured trauma-induced Treg activation in MHC class II gene deficient (MHCII−/−) mice or in mice that were given Fab fragment of anti-MHC class II antibody to block TCR activation. Injury-induced Treg activation occurred in normal mice but only partial activation was detected in MHCII−/− mice or in mice that were given Fab anti-MHCII antibody. These findings demonstrate that trauma activates a memory-like Treg subpopulation and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism.