Ha Grace K, Pastrana Marlon, Huang Zhi, Petitto John M
Department of Psychiatry, University of Florida, Gainesville, FL, USA.
Neurosci Lett. 2008 Oct 10;443(3):150-4. doi: 10.1016/j.neulet.2008.07.067. Epub 2008 Jul 31.
T cells have the ability to mount a memory response to a previously encountered antigen such that re-exposure to the antigen results in a response that is greater in magnitude and function. Following facial nerve transection, T cells have been shown to traffic to injured motor neurons in the facial motor nucleus (FMN) and may have the ability to promote neuronal survival and functional recovery. Previously, we demonstrated that early exposure to neuronal injury on one side of the brain during young adulthood elicited a T cell response that was greater in magnitude following exposure to the same form of injury on the contralateral side later in adulthood. Whether the T cell memory response to neuronal injury influenced functional recovery following nerve crush injury was unknown. In the current study, we tested the hypotheses that (1) transection of the right facial nerve in sensitized mice would result in faster recovery of the whisker response when the contralateral facial nerve is crushed 10 weeks later, and (2) the early recovery would be associated with an increase in the magnitude of the T cell response in the contralateral FMN following crush injury in sensitized mice. The onset of modest recovery in sensitized mice occurred between 3 and 5 days following crush injury of the contralateral facial nerve, approximately 1.5 days earlier than naïve mice, and was associated with more than a two-fold increase in the magnitude of the T cell response in the contralateral FMN following crush injury. There was no difference between groups in the number of days to full recovery. Further study of how T cell memory influences neuroregeneration may have important implications for translational research.
T细胞具有对先前遇到的抗原产生记忆反应的能力,因此再次接触该抗原会导致反应在强度和功能上更强烈。面神经横断后,T细胞已被证明会迁移至面神经运动核(FMN)中受损的运动神经元,并且可能具有促进神经元存活和功能恢复的能力。此前,我们证明,成年早期一侧大脑早期暴露于神经元损伤会引发T细胞反应,成年后期对侧暴露于相同形式的损伤后,该反应强度会更大。T细胞对神经元损伤的记忆反应是否会影响神经挤压伤后的功能恢复尚不清楚。在本研究中,我们检验了以下假设:(1)致敏小鼠右侧面神经横断后,10周后对侧面神经挤压时,触须反应恢复更快;(2)早期恢复与致敏小鼠挤压伤后对侧FMN中T细胞反应强度增加有关。致敏小鼠适度恢复的开始时间发生在对侧面神经挤压伤后3至5天之间,比未致敏小鼠早约1.5天,并且与挤压伤后对侧FMN中T细胞反应强度增加两倍以上有关。各组完全恢复所需天数没有差异。进一步研究T细胞记忆如何影响神经再生可能对转化研究具有重要意义。