Tan L, Gordon K B, Mueller J P, Matis L A, Miller S D
Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611, USA.
J Immunol. 1998 May 1;160(9):4271-9.
There is controversy regarding the possible role of glial cells as APCs in the pathogenesis of central nervous system (CNS) demyelinating diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Microglia have been clearly shown to present Ag in the CNS, and due to the proximity of activated astroglial cells to infiltrating T cells and macrophages in demyelinating lesions, it is also possible that astrocytes positively or negatively regulate disease initiation and/or progression. We examined the capacity of IFN-gamma-treated astrocytes from EAE-susceptible SJL/J mice to process and present myelin epitopes. IFN-gamma activation up-regulated ICAM-1, VCAM-1, MHC class II, invariant chain, H2-M, CD40, and B7-1 as determined by FACS and/or RT-PCR analyses. B7-2 expression was only marginally enhanced on SJL/J astrocytes. Consistent with the expression of these accessory molecules, IFN-gamma-treated SJL/J astrocytes induced the B7-1-dependent activation of Th1 lines and lymph node T cells specific for the immunodominant encephalitogenic proteolipid protein (PLP) epitope (PLP139-151) as assessed by proliferation and activation for the adoptive transfer of EAE. Interestingly, IFN-gamma-activated astrocytes efficiently processed and presented PLP139-151, but not the subdominant PLP178-191, PLP56-70, or PLP104-117 epitopes, from intact PLP and a recombinant variant fusion protein of PLP (MP4). The data are consistent with the hypothesis that astrocytes in the proinflammatory CNS environment have the capability of activating CNS-infiltrating encephalitogenic T cells specific for immunodominant epitopes on various myelin proteins that may be involved in either the initial or the relapsing stages of EAE.
关于神经胶质细胞作为抗原呈递细胞（APC）在中枢神经系统（CNS）脱髓鞘疾病（如多发性硬化症及其动物模型实验性自身免疫性脑脊髓炎（EAE））发病机制中的可能作用存在争议。小胶质细胞已被明确证明在中枢神经系统中呈递抗原，并且由于在脱髓鞘病变中活化的星形胶质细胞与浸润的T细胞和巨噬细胞接近，星形胶质细胞也有可能正向或负向调节疾病的起始和/或进展。我们检测了来自易患EAE的SJL/J小鼠经γ干扰素处理的星形胶质细胞处理和呈递髓鞘表位的能力。通过流式细胞术和/或逆转录-聚合酶链反应分析确定，γ干扰素激活上调了细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）、主要组织相容性复合体II类分子、恒定链、H2-M、CD40和B7-1。B7-2在SJL/J星形胶质细胞上的表达仅略有增强。与这些辅助分子的表达一致，经γ干扰素处理的SJL/J星形胶质细胞诱导了Th1细胞系和针对免疫显性致脑炎性蛋白脂蛋白（PLP）表位（PLP139-151）的淋巴结T细胞的B7-1依赖性活化，这通过增殖和活化来评估，用于EAE的过继转移。有趣的是，经γ干扰素激活的星形胶质细胞有效地处理并呈递了PLP139-151，但未处理并呈递来自完整PLP和PLP重组变体融合蛋白（MP4）的次要PLP178-191、PLP56-70或PLP104-117表位。这些数据与以下假设一致：在促炎性中枢神经系统环境中的星形胶质细胞有能力激活中枢神经系统浸润的、针对各种髓鞘蛋白上免疫显性表位的致脑炎性T细胞，这些表位可能参与EAE的初始或复发阶段。
