Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
J Neuroimmune Pharmacol. 2009 Dec;4(4):462-75. doi: 10.1007/s11481-009-9166-2. Epub 2009 Aug 11.
While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.
虽然中枢神经系统（CNS）曾经被认为是免疫细胞无法监测到的，这一概念被称为“免疫特权”，但现在很清楚，免疫反应确实会发生在 CNS 中——这就产生了神经免疫学领域。这些 CNS 免疫反应可以由内源性（神经胶质）和/或外源性（外周白细胞）来源驱动，并可以发挥有产性或病理性作用。来自小鼠模型的最新证据支持这样一种观点，即外周单核细胞/巨噬细胞的浸润限制了阿尔茨海默病病理的进展，并抵抗西尼罗河病毒脑炎。此外，浸润的 T 淋巴细胞可能有助于在肌萎缩侧索硬化症模型中减轻神经元丢失。另一方面，CNS 白细胞渗透驱动实验性自身免疫性脑脊髓炎（一种用于人类脱髓鞘疾病多发性硬化症的小鼠模型），并且在帕金森病和人类免疫缺陷病毒脑炎中也可能是病理性的。对于负责将免疫细胞从外周转移到患病的 CNS 的细胞和分子机制的关键理解将是针对这些细胞进行神经退行性疾病治疗干预的关键，从而允许神经再生过程发生。
