Rao K, Lund R D
Department of Neurobiology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
J Comp Neurol. 1993 Oct 22;336(4):613-27. doi: 10.1002/cne.903360413.
The brain has long been considered to be an immunologically privileged site. However, privilege is not absolute, as has been shown by the inability of foreign tissue grafts to survive indefinitely in the brain. The rejection of this tissue is accompanied by the upregulation of major histocompatibility complex (MHC) antigen expression. Therefore it is essential to define conditions that influence the expression of these antigens in the brain, especially since such a definition may further the understanding of disease processes that lead to the autoimmune destruction of the central nervous system. Here we show that both MHC class I and class II antigens are expressed within 1 or 2 days of eye removal by cells showing the morphological characteristics of microglia. Expression is seen along the optic pathway and within the brainstem centers to which optic axons project. In the early stages of the reaction, MHC class I antigen expression is seen throughout the optic pathway, including the terminal distribution areas of the subcortical visual centers, while MHC cells class II are localised mainly to degenerating myelinated fiber systems. These changes are not accompanied by any alteration in the integrity of the blood-brain barrier. During the second week postlesion, class I positive cells are found beyond the confines of the degenerating pathways, while class II positive cells are seen within regions such as the stratum griseum superficiale of the superior colliculus, where few myelinated axons are present. There is subsequent diminution of MHC positive cells, but a small number of cells are still seen 60 days post-lesion. Focal lesions within the eye show that at early survival times, while class I MHC positive cells are distributed throughout the nerve, class II positive cells are largely absent from the unmyelinated segment of the nerve. Retrograde changes in the retina after nerve section are accompanied only by MHC class I antigen expression. These observations show that neural degeneration is accompanied by a rigid sequence of events involving expression of MHC antigens by microglia. If foreign antigens were present in the brain while these events were taking place, it is possible that such antigens would be recognised and destroyed by the host immune system.
长期以来，大脑一直被认为是一个免疫特惠部位。然而，这种特惠并非绝对，这已通过异体组织移植无法在大脑中无限期存活得到证明。这种组织的排斥伴随着主要组织相容性复合体（MHC）抗原表达的上调。因此，确定影响大脑中这些抗原表达的条件至关重要，特别是因为这样的定义可能有助于进一步理解导致中枢神经系统自身免疫性破坏的疾病过程。在此我们表明，在眼球摘除后1或2天内，显示小胶质细胞形态特征的细胞即可表达MHC I类和II类抗原。在视通路以及视神经轴突投射到的脑干中枢内均可观察到这种表达。在反应的早期阶段，在整个视通路中都可看到MHC I类抗原表达，包括皮层下视觉中枢的终末分布区域，而MHC II类细胞主要定位于退化的有髓纤维系统。这些变化并未伴随血脑屏障完整性的任何改变。在损伤后的第二周，I类阳性细胞出现在退化通路范围之外，而II类阳性细胞则出现在诸如上丘浅层灰质等几乎没有有髓轴突的区域。随后MHC阳性细胞数量减少，但在损伤后60天仍可看到少量细胞。眼内的局灶性损伤表明，在早期存活阶段，虽然I类MHC阳性细胞分布于整个神经，但II类阳性细胞在神经的无髓段基本不存在。神经切断后视网膜的逆行性变化仅伴有MHC I类抗原表达。这些观察结果表明，神经变性伴随着一系列严格的事件，包括小胶质细胞表达MHC抗原。如果在这些事件发生时大脑中存在外来抗原，那么这些抗原有可能被宿主免疫系统识别并破坏。
