Malone Karen E, Stohlman Stephen A, Ramakrishna Chandran, Macklin Wendy, Bergmann Cornelia C
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Glia. 2008 Mar;56(4):426-35. doi: 10.1002/glia.20625.
Glia exhibit differential susceptibility to CD8 T cell mediated effector mechanisms during neurotropic coronavirus infection. In contrast to microglia, oligodendroglia are resistant to CD8 T cell perforin-mediated viral control in the absence of IFN gamma. Kinetic induction of MHC Class I expression by microglia and oligodendroglia in vivo was thus analyzed to assess responses to distinct inflammatory signals. Flow cytometry demonstrated delayed Class I surface expression by oligodendroglia compared with microglia. Distinct kinetics of Class I protein upregulation correlated with cell type specific transcription patterns of genes encoding Class I heavy chains and antigen processing components. Microglia isolated from naïve mice expressed high levels of these mRNAs, whereas they were near detection limits in oligodendroglia; nevertheless, Class I protein was undetectable on both cell types. Infection induced modest mRNA increases in microglia, but dramatic transcriptional upregulation in oligodendroglia coincident with IFN alpha or IFN gamma mRNA increases in infected tissue. Ultimately mRNAs reached similar levels in both cell types at their respective time points of maximal Class I expression. Expression of Class I on microglia, but not oligodendroglia, in infected IFN gamma deficient mice supported distinct IFN requirements for Class I presentation. These data suggest an innate immune preparedness of microglia to present antigen and engage CD8 T cells early following infection. The delayed, yet robust, IFN gamma dependent capacity of oligodendroglia to express Class I suggests strict control of immune interactions to avoid CD8 T cell recognition and potential presentation of autoantigen to preserve myelin maintenance.
在嗜神经性冠状病毒感染期间，神经胶质细胞对CD8 T细胞介导的效应机制表现出不同的敏感性。与小胶质细胞不同，在缺乏干扰素γ的情况下，少突胶质细胞对CD8 T细胞穿孔素介导的病毒控制具有抗性。因此，分析了体内小胶质细胞和少突胶质细胞对MHC I类表达的动力学诱导，以评估对不同炎症信号的反应。流式细胞术显示，与小胶质细胞相比，少突胶质细胞的I类表面表达延迟。I类蛋白上调的不同动力学与编码I类重链和抗原加工成分的基因的细胞类型特异性转录模式相关。从新生小鼠分离的小胶质细胞表达高水平的这些mRNA，而在少突胶质细胞中它们接近检测极限；然而，两种细胞类型均未检测到I类蛋白。感染导致小胶质细胞中mRNA适度增加，但少突胶质细胞中出现显著的转录上调，同时感染组织中干扰素α或干扰素γ mRNA增加。最终，在各自I类表达的最大时间点，两种细胞类型中的mRNA达到相似水平。在感染的干扰素γ缺陷小鼠中，I类在小胶质细胞而非少突胶质细胞上的表达支持了I类呈递对不同干扰素的需求。这些数据表明，小胶质细胞具有先天免疫准备，能够在感染后早期呈递抗原并与CD8 T细胞相互作用。少突胶质细胞延迟但强大的依赖干扰素γ表达I类的能力表明，对免疫相互作用进行严格控制，以避免CD8 T细胞识别和自身抗原的潜在呈递，从而维持髓鞘的完整性。
