Laboratory of Behavioral Neuroimmunology, Department of Psychiatry, University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF Building Room 934E, Baltimore, MD, 21201, USA.
Research and Development Service, Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, USA.
Eur J Neurosci. 2018 Apr;47(8):968-978. doi: 10.1111/ejn.13860. Epub 2018 Feb 23.
Accumulating evidence has shown that lymphocytes modulate behaviour and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune-deficient mice restores a number of neurobehavioural deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behaviour during development remains unknown. In this study, neonate lymphocyte-deficient Rag2 mice were reconstituted within 48 hours after birth with lymphoid cells from transgenic donors expressing green fluorescent protein, allowing for their identification in various tissues in recipient mice while retaining all functional aspects. Adolescent Rag2 and reconstituted Rag2 along with C57BL/6J wild-type mice underwent a series of behavioural tests, including open field, social interaction and sucrose preference tests. At 12 weeks, they were evaluated in the Morris water maze (MWM). Reconstituted mice showed changes in almost all aspects of behaviour that were assessed, with a remarkable complete rescue of impaired social behaviour displayed by adolescent Rag2 mice. Consistent with previous reports in adult mice, neonatal reconstitution in Rag2 mice restored spatial memory in the MWM. The presence of donor lymphocytes in the brain of neonatally reconstituted Rag2 mice was confirmed at various developmental points. These findings provide evidence that lymphocytes colonize the brain during post-natal development and modulate behaviour across the lifespan supporting a role for adaptive immunity during brain maturation.
越来越多的证据表明，淋巴细胞通过与中枢神经系统的直接相互作用来调节行为和认知。研究表明，通过从野生型向免疫缺陷小鼠中过继转移淋巴细胞来重建，可以恢复这些模型中观察到的许多神经行为缺陷。此外，已经表明这些效应主要是由 T 淋巴细胞介导的。迄今为止，过继转移研究使用成年小鼠，但淋巴细胞是否也可以在发育过程中调节行为仍不清楚。在这项研究中，新生淋巴细胞缺陷 Rag2 小鼠在出生后 48 小时内用表达绿色荧光蛋白的转基因供体的淋巴细胞进行重建，允许在受体小鼠的各种组织中识别它们，同时保留所有功能方面。青春期 Rag2 和重建 Rag2 以及 C57BL/6J 野生型小鼠接受了一系列行为测试，包括旷场、社会互动和蔗糖偏好测试。在 12 周时，它们在 Morris 水迷宫 (MWM) 中进行了评估。重建小鼠在评估的几乎所有行为方面都发生了变化，青春期 Rag2 小鼠受损的社会行为得到了显著完全的恢复。与成年小鼠的先前报道一致，Rag2 小鼠中的新生重建恢复了 MWM 中的空间记忆。在不同的发育阶段证实了新生 Rag2 小鼠大脑中存在供体淋巴细胞。这些发现提供了证据，表明淋巴细胞在出生后发育过程中定植于大脑，并调节整个生命周期的行为，支持适应性免疫在大脑成熟过程中的作用。
