Salek-Ardakani Shahram, Lyons Stephen A, Arrand John R
Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Withington, Manchester, UK.
J Immunol. 2004 Jul 1;173(1):321-31. doi: 10.4049/jimmunol.173.1.321.
The role of monocytes and macrophages during EBV infection is not clear. The interaction of EBV with human monocytes was investigated in terms of cell survival and morphological and phenotypic changes to gain a better understanding of the role of these cells during EBV infection. We show that EBV infection of PBMCs rescues monocytes from undergoing spontaneous apoptosis and dramatically enhances their survival. Results obtained with heat-inactivated virus, neutralizing anti-EBV mAb 72A1 and recombinant gp350, suggest that enhancement of viability by EBV requires both infectious virus and interaction between gp350 and its receptor. IFN-alpha either secreted within 24 h from PBMCs upon infection with EBV or exogenously added to unstimulated monocytes inhibited spontaneous apoptosis, indicating that induction of IFN-alpha is an early important survival signal responsible for the delay in the apoptosis of monocytes. EBV infection also induced acute maturation of monocytes to macrophages with morphological and phenotypic characteristics of potent APCs. Monocytes exposed to EBV became larger in size with increased granularity and expressed considerably higher levels of membrane HLA classes I and II, ICAM-1, CD80, CD86, and CD40 compared with uninfected cultures. These observations provide the first immunoregulatory links among EBV, IFN-alpha, and monocyte survival and maturation and importantly raise the possibility that these cells may serve as a vehicle for the dissemination of the virus as well as being active participants in eliciting anti-EBV T cell responses during acute infection.
单核细胞和巨噬细胞在EB病毒感染过程中的作用尚不清楚。我们从细胞存活以及形态和表型变化方面研究了EB病毒与人类单核细胞的相互作用，以便更好地了解这些细胞在EB病毒感染过程中的作用。我们发现，外周血单核细胞（PBMCs）感染EB病毒可使单核细胞免于自发凋亡，并显著提高其存活率。用热灭活病毒、中和性抗EB病毒单克隆抗体72A1和重组gp350获得的结果表明，EB病毒增强细胞活力既需要感染性病毒，也需要gp350与其受体之间的相互作用。EB病毒感染后24小时内PBMCs分泌的或外源性添加到未刺激单核细胞中的干扰素-α（IFN-α）可抑制自发凋亡，这表明IFN-α的诱导是一个早期重要的存活信号，负责延迟单核细胞的凋亡。EB病毒感染还可诱导单核细胞急性成熟为巨噬细胞，这些巨噬细胞具有高效抗原呈递细胞（APCs）的形态和表型特征。与未感染的培养物相比，暴露于EB病毒的单核细胞体积增大、颗粒度增加，并且膜表面HLA I类和II类分子、细胞间黏附分子-1（ICAM-1）、CD80、CD86和CD40的表达水平显著升高。这些观察结果首次揭示了EB病毒、IFN-α与单核细胞存活和成熟之间的免疫调节联系，并且重要的是提出了一种可能性，即这些细胞可能作为病毒传播的载体，以及在急性感染期间引发抗EB病毒T细胞反应的积极参与者。
