Cowan E P, Pierce M L, Dhib-Jalbut S
Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892.
J Neuroimmunol. 1991 Jul;33(1):17-28. doi: 10.1016/0165-5728(91)90030-b.
Antigens encoded within the major histocompatibility complex (MHC) are not normally expressed in the central nervous system (CNS), but can be induced by treatment with interferon-gamma (IFN-gamma). Other cytokines released during an inflammatory process can potentially influence MHC expression as well. One cytokine of interest is interleukin-1 (IL-1), an immunoregulatory polypeptide that is produced by macrophages and also by cells in the CNS. In this study, the effect of IL-1 beta on MHC expression in a human glioblastoma multiforme cell line, U-105 MG, has been examined. Treatment of U-105 MG with 10 U IL-1 beta/ml for a period of 5 days resulted in a decrease in constitutive cell surface HLA class II expression and limited the induction of class II by IFN-gamma. This effect was also observed on steady-state levels of class II RNA and could be neutralized with antibodies to IL-1 beta. All class II transcripts examined (HLA-DR, -DQ, and -DP alpha and beta) were affected. Class I expression was only marginally changed by IL-1 beta treatment. A minimal concentration of 1 U IL-1 beta/ml was required to reduce class II expression and a kinetics experiment indicated that U-105 MG must be treated for at least 4 days with IL-1 beta for a decrease in class II expression to be observed. This study suggests that IL-1 may play a role in limiting immunoreactivity in the CNS by limiting class II induction.
主要组织相容性复合体(MHC)编码的抗原通常不在中枢神经系统(CNS)中表达,但可通过用γ干扰素(IFN-γ)处理来诱导表达。炎症过程中释放的其他细胞因子也可能影响MHC的表达。一种值得关注的细胞因子是白细胞介素-1(IL-1),它是一种免疫调节多肽,由巨噬细胞以及CNS中的细胞产生。在本研究中,检测了IL-1β对人多形性胶质母细胞瘤细胞系U-105 MG中MHC表达的影响。用10 U IL-1β/ml处理U-105 MG 5天,导致组成型细胞表面HLA II类表达降低,并限制了IFN-γ对II类的诱导。在II类RNA的稳态水平上也观察到了这种效应,并且可以用抗IL-1β抗体中和。所有检测的II类转录本(HLA-DR、-DQ和-DPα及β)均受影响。IL-1β处理对I类表达的影响很小。降低II类表达需要的最小浓度为1 U IL-1β/ml,动力学实验表明,U-105 MG必须用IL-1β处理至少4天才能观察到II类表达的降低。这项研究表明,IL-1可能通过限制II类诱导在限制CNS中的免疫反应性方面发挥作用。