Salek-Ardakani Shahram, Arrand John R, Mackett Mike
Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester, M20 9BX United Kingdom.
Virology. 2002 Dec 20;304(2):342-51. doi: 10.1006/viro.2002.1716.
Monocytes and macrophages play a central role in viral infections, as a target for viruses and in activation of both innate and adaptive immune responses. Epstein-Barr virus (EBV) has evolved elaborate strategies to dampen the immune system and to persist within the host. There is evidence that the product of the BCRF-1 open reading frame of EBV, viral interleukin-10 (vIL-10), inhibits the capacity of monocytes/macrophages to induce T cell activation, but the full mechanism of this effect is unknown. To determine whether this effect might involve modulation of the expression of accessory molecules known to be important in T cell activation, we analyzed by flow cytometry the influence of vIL-10 on the basal as well as on IFN-gamma-induced up-regulation of HLA molecules, ICAM-1, and two members of the B7 family B7.1 (CD80) and B7.2 (CD86) at the surface of human monocytes. Viral IL-10 in a concentration-dependent manner inhibited both basal- and IFN-gamma-induced HLA-class II, ICAM-1 (basal levels of ICAM-2 and ICAM-3 is unaffected), CD80, and CD86 up-regulation when added simultaneously with IFN-gamma. In contrast, complete inhibition of HLA-class I expression on monocytes/macrophages occurred only when vIL-10 was present 2 h prior to the addition of IFN-gamma, implying that vIL-10 affects an early step in the IFN-gamma signaling pathway. As both monocytes and macrophages can be infected by EBV, we propose that vIL-10-mediated impairment of monocyte/macrophage antigen-presenting function could help the virus-infected cells to avoid detection by the host's T cells on one hand and contribute to its immunosuppressive properties on the other.
单核细胞和巨噬细胞在病毒感染中发挥着核心作用，既是病毒的靶细胞，又参与激活先天性和适应性免疫反应。爱泼斯坦-巴尔病毒（EBV）已进化出复杂的策略来抑制免疫系统并在宿主体内持续存在。有证据表明，EBV的BCRF-1开放阅读框产物，即病毒白细胞介素-10（vIL-10），可抑制单核细胞/巨噬细胞诱导T细胞活化的能力，但其作用的完整机制尚不清楚。为了确定这种效应是否可能涉及调节已知在T细胞活化中起重要作用的辅助分子的表达，我们通过流式细胞术分析了vIL-10对人单核细胞表面HLA分子、细胞间黏附分子-1（ICAM-1）以及B7家族的两个成员B7.1（CD80）和B7.2（CD86）的基础表达以及γ干扰素诱导的上调表达的影响。当与γ干扰素同时添加时，病毒白细胞介素-10以浓度依赖的方式抑制基础和γ干扰素诱导的HLA-II类分子、ICAM-1（ICAM-2和ICAM-3的基础水平不受影响）、CD80和CD86的上调表达。相反，仅当在添加γ干扰素前2小时存在vIL-10时，单核细胞/巨噬细胞上的HLA-I类分子表达才会完全受到抑制，这意味着vIL-10影响γ干扰素信号通路中的早期步骤。由于单核细胞和巨噬细胞都可被EBV感染，我们认为vIL-10介导的单核细胞/巨噬细胞抗原呈递功能受损一方面有助于病毒感染细胞逃避宿主T细胞的检测，另一方面有助于其免疫抑制特性。
