Gehrmann J, Banati R B, Kreutzberg G W
Max-Planck-Institute of Psychiatry, Department of Neuromorphology, Martinsried near Munich, Germany.
J Neuroimmunol. 1993 Nov-Dec;48(2):189-98. doi: 10.1016/0165-5728(93)90191-z.
The degree of MHC class II expression in histologically normal human brain biopsy or autopsy tissue is still controversial. According to the generally held view MHC class II expression is rather low in the normal brain with the exception of the white matter. In the present study, HLA-DR expression was examined immunocytochemically in different brain areas obtained from three autopsy cases with short post-mortem times (i.e. 6 h). Based on standard histological evaluation, the brain areas studied appeared as histologically normal tissue. In all brain areas there was a strong constitutive HLA-DR expression on ramified microglia. The number of HLA-DR-immunoreactive microglia was strongest in the white matter (the corpus callosum and the capsula interna for example). The border zone between white matter and grey matter, however, revealed a sharp contrast between a high density of HLA-DR-immunoreactive microglia in the white matter and a rather low number in the grey matter. In the grey matter, HLA-DR-immunoreactive microglia were much less frequent than in the white matter and more pronounced on perivascular cells. The staining and distribution pattern of HLA-DR-immunoreactive microglia was confirmed by immunocytochemistry with a panel of different anti-HLA-DR monoclonal antibodies as well as by quantitative analysis of the immunostaining. Unlike the HLA-DR immunoreactivity, HLA-ABC immunoreactivity (detecting MHC class I antigens) was confined to endothelia and not observed on microglia. In the choroid plexus stromal macrophages expressed both class I and II antigens (i.e. at a location which could provide the peripheral immune system access to CNS antigens). Constitutive HLA-DR expression by microglia qualifies them as the main resident antigen-presenting cell of the brain. The pronounced overall HLA-DR expression by resting microglia questions a central dogma of the brain as an immune-privileged site and further points to the key role of the microglia in brain immune surveillance.
在组织学上正常的人脑活检或尸检组织中，MHC II类分子的表达程度仍存在争议。根据普遍观点，除了白质外，正常脑中MHC II类分子的表达相当低。在本研究中，采用免疫细胞化学方法检测了3例死后时间较短（即6小时）的尸检病例不同脑区的HLA-DR表达。基于标准组织学评估，所研究的脑区表现为组织学上正常的组织。在所有脑区，分支状小胶质细胞均有强烈的组成性HLA-DR表达。HLA-DR免疫反应性小胶质细胞数量在白质中最多（例如胼胝体和内囊）。然而，白质和灰质之间的边界区域显示出鲜明对比，白质中HLA-DR免疫反应性小胶质细胞密度高，而灰质中数量相当少。在灰质中，HLA-DR免疫反应性小胶质细胞比白质中少见，且在血管周围细胞上更明显。用一组不同的抗HLA-DR单克隆抗体进行免疫细胞化学以及对免疫染色进行定量分析，证实了HLA-DR免疫反应性小胶质细胞的染色和分布模式。与HLA-DR免疫反应性不同，HLA-ABC免疫反应性（检测MHC I类抗原）局限于内皮细胞，在小胶质细胞上未观察到。在脉络丛中，基质巨噬细胞同时表达I类和II类抗原（即在一个可使外周免疫系统接触中枢神经系统抗原的位置）。小胶质细胞组成性HLA-DR表达使其成为脑内主要的常驻抗原呈递细胞。静息小胶质细胞明显的整体HLA-DR表达对脑作为免疫豁免部位这一核心教条提出了质疑，并进一步指出了小胶质细胞在脑免疫监视中的关键作用。
