Sun D, Wekerle H
Nature. 1986;320(6057):70-2. doi: 10.1038/320070a0.
T lymphocytes specific for myelin basic protein (MBP) are responsible for the cellular events leading to autoimmune disease within the central (CNS) and peripheral (PNS) nervous systems. Both in actively induced and T-cell transfer versions of experimental autoimmune encephalomyelitis (EAE) and neuritis (EAN), the autoaggressive T cells are activated outside the nervous system and reach their target tissue via the blood circulation. The target specificity of the autoaggressive T cells is impressive; T-cell lines specific for MBP predominantly home to and affect the white matter of the CNS whereas T cells specific for PNS myelin protein P2 exclusively infiltrate peripheral nerves. Having penetrated the tight blood tissue barriers, the lymphocytes seem to interact with local cells expressing the relevant autoantigen in an immunogenic form. Although the exact mechanism of target finding and destruction is unknown, studies from our laboratory have shown that astrocytes, a main component of the normal CNS glia, can actively present antigen to specific T cells. This observation suggests that astrocytes are involved in natural immune reactivity within the CNS, and that they may be involved in pathological aberrations, such as in the development of autoimmune lesions. Having studied astrocyte/T-cell interactions in more detail, we discovered that encephalitogenic T-cell lines recognizing MBP on astrocytes will subsequently proceed to kill the presenting cells. Here we report that astrocyte killing follows the rules governing 'classical' T-cell-mediated cytolysis; it is antigen-specific, restricted by antigens of the major histocompatibility complex (MHC) and apparently contact-dependent. Our data suggest that the nature of the recognized antigenic epitope determines whether or not antigen recognition is followed by killing; moreover, killing of antigen-presenting astrocytes seems to be correlated with the capacity to transfer encephalomyelitis to normal syngeneic rats.
针对髓鞘碱性蛋白（MBP）的T淋巴细胞，是导致中枢神经系统（CNS）和外周神经系统（PNS）自身免疫性疾病的细胞活动的罪魁祸首。在实验性自身免疫性脑脊髓炎（EAE）和神经炎（EAN）的主动诱导和T细胞转移模型中，自身攻击性T细胞均在神经系统外被激活，并通过血液循环到达其靶组织。自身攻击性T细胞的靶标特异性令人瞩目；针对MBP的T细胞系主要归巢于并影响CNS的白质，而针对PNS髓鞘蛋白P2的T细胞则仅浸润外周神经。淋巴细胞穿透紧密的血液组织屏障后，似乎会与以免疫原性形式表达相关自身抗原的局部细胞相互作用。尽管靶标识别和破坏的确切机制尚不清楚，但我们实验室的研究表明，星形胶质细胞作为正常CNS神经胶质的主要成分，能够主动将抗原呈递给特定的T细胞。这一观察结果表明，星形胶质细胞参与了CNS内的天然免疫反应，并且它们可能参与了病理异常，例如自身免疫性病变的发展。在更详细地研究了星形胶质细胞/T细胞相互作用后，我们发现识别星形胶质细胞上MBP的致脑炎性T细胞系随后会继续杀死呈递细胞。在此我们报告，星形胶质细胞的杀伤遵循“经典”T细胞介导的细胞溶解规则；它是抗原特异性的，受主要组织相容性复合体（MHC）抗原的限制，并且显然依赖于细胞接触。我们的数据表明，所识别的抗原表位的性质决定了抗原识别后是否会发生杀伤；此外，抗原呈递星形胶质细胞的杀伤似乎与将脑脊髓炎转移至正常同基因大鼠的能力相关。
