Risau W, Engelhardt B, Wekerle H
Max-Planck-Institute for Psychiatry, Martinsried, FRG.
J Cell Biol. 1990 May;110(5):1757-66. doi: 10.1083/jcb.110.5.1757.
The endothelial blood-brain barrier (BBB) has a critical role in controlling lymphocyte traffic into the central nervous system (CNS), both in physiological immunosurveillance, and in its pathological aberrations. The intercellular signals that possibly could induce lymphocytes to cross the BBB include immunogenic presentation of protein (auto-)antigens by BBB endothelia to circulating T lymphocytes. This concept has raised much, though controversial, attention. We approached this problem by analyzing in vitro immunospecific interactions between clonal rat T lymphocyte lines with syngeneic, stringently purified endothelial monolayer cultures from adult brain micro-vessels. The rat brain endothelia (RBE) were established from rat brain capillaries using double collagenase digestion, density gradient fractionation and selective cytolysis of contaminating pericytes by anti-Thy 1.1 antibodies and complement. Incubation with interferon-gamma in most of the brain-derived endothelial cells induced Ia-antigens in the cytoplasm and on the cell surface in some of the cells. Before the treatment, the cells were completely Ia-negative. Pericytes were unresponsive to IFN-gamma treatment. When confronted with syngeneic T cell lines specific for protein (auto-)antigens (e.g., ovalbumin and myelin basic protein, MBP), RBE were completely unable to induce antigen-specific proliferation of syngeneic T lymphocytes irrespective of pretreatment with IFN-gamma and of cell density. RBE were inert towards the T cells, and did not suppress T cell activation induced by other "professional" antigen presenting cells (APC) such as thymus-derived dendritic cells or macrophages. IFN-gamma-treated RBE were, however, susceptible to immunospecific T cell killing. They were lysed by MBP-specific T cells in the presence of the specific antigen or Con A. Antigen dependent lysis was restricted by the appropriate (MHC) class II product. We conclude that the interaction of brain endothelial cells with encephalitogenic T lymphocytes may involve recognition of antigen in the molecular context of relevant MHC products, but that this interaction per se is insufficient to initiate the full T cell activation program.
内皮血脑屏障（BBB）在控制淋巴细胞进入中枢神经系统（CNS）方面起着关键作用，无论是在生理免疫监视还是在其病理异常情况下。可能诱导淋巴细胞穿越血脑屏障的细胞间信号包括血脑屏障内皮细胞向循环T淋巴细胞进行蛋白质（自身）抗原的免疫原性呈递。这一概念引起了很多关注，尽管存在争议。我们通过分析克隆大鼠T淋巴细胞系与来自成年脑微血管的同基因、严格纯化的内皮单层培养物之间的体外免疫特异性相互作用来解决这个问题。大鼠脑内皮细胞（RBE）是通过双胶原酶消化、密度梯度分级分离以及用抗Thy 1.1抗体和补体对污染的周细胞进行选择性细胞溶解从大鼠脑毛细血管中建立的。在大多数脑源性内皮细胞中用干扰素-γ孵育会在一些细胞的细胞质和细胞表面诱导Ia抗原。在处理之前，细胞完全为Ia阴性。周细胞对干扰素-γ处理无反应。当与针对蛋白质（自身）抗原（例如卵清蛋白和髓鞘碱性蛋白，MBP）的同基因T细胞系相遇时，无论是否用干扰素-γ预处理以及细胞密度如何，RBE完全无法诱导同基因T淋巴细胞的抗原特异性增殖。RBE对T细胞无反应，并且不抑制由其他“专业”抗原呈递细胞（APC）如胸腺来源的树突状细胞或巨噬细胞诱导的T细胞活化。然而，经干扰素-γ处理的RBE易受免疫特异性T细胞杀伤。在存在特异性抗原或刀豆蛋白A的情况下，它们会被MBP特异性T细胞裂解。抗原依赖性裂解受到适当的（MHC）II类产物的限制。我们得出结论，脑内皮细胞与致脑炎T淋巴细胞的相互作用可能涉及在相关MHC产物的分子背景下对抗原的识别，但这种相互作用本身不足以启动完整的T细胞活化程序。
