Selgrade M K, Daniels M J, Hu P C, Miller F J, Graham J A
Infect Immun. 1982 Dec;38(3):1046-55. doi: 10.1128/iai.38.3.1046-1055.1982.
The effects of cyclophosphamide (CY) treatment on acute murine cytomegalovirus (MCMV) infection were studied to explore the potential usefulness of MCMV as a means of detecting immune dysfunction and to identify host defense mechanisms important for protection against MCMV. Conditions found optimal for enhancing MCMV infection with CY included infecting adult mice with 2 X 10(5) PFU or more of virus and administering 80 mg or more of CY per kg 1 to 3 days later. In addition to enhanced mortality, virus titers in lung, liver, and spleen were elevated in CY-treated mice, and wet weights of liver, spleen, and thymus were depressed when compared with those of infected but untreated mice. Treatment with CY before MCMV challenge was not as efficient a means of enhancing mortality as treatment after virus challenge. The effect that the time of CY administration relative to infection had on mortality correlated with the effect of such timing on natural killer cell activity. Animals treated before infection exhibited depressed natural killer cell activity initially. However, they rapidly recovered this response, and by 5 days postinfection they had the same level of virus-augmented activity seen in untreated mice. In contrast, animals treated after infection did not recover natural killer cell activity and were more likely to die. A similar correlation was not obtained when the effects of CY on lymphocyte responses to B and T cell mitogens were examined, nor were there striking differences in pathology between the treatment groups. The data suggest an important role for natural killer cells in host defense against MCMV. Also, increased susceptibility to MCMV may provide a useful indicator of deficits in the natural killer cell response.
研究了环磷酰胺（CY）治疗对急性小鼠巨细胞病毒（MCMV）感染的影响，以探索MCMV作为检测免疫功能障碍手段的潜在用途，并确定对抵御MCMV至关重要的宿主防御机制。发现用CY增强MCMV感染的最佳条件包括用2×10⁵ PFU或更多病毒感染成年小鼠，并在1至3天后每千克给予80 mg或更多的CY。除了死亡率增加外，CY处理的小鼠肺、肝和脾中的病毒滴度升高，与感染但未处理的小鼠相比，肝、脾和胸腺的湿重降低。在MCMV攻击前用CY治疗作为增加死亡率的手段不如在病毒攻击后治疗有效。CY给药时间相对于感染时间对死亡率的影响与这种时间安排对自然杀伤细胞活性的影响相关。感染前接受治疗的动物最初表现出自然杀伤细胞活性降低。然而，它们迅速恢复了这种反应，到感染后5天时，它们具有与未处理小鼠相同水平的病毒增强活性。相比之下，感染后接受治疗的动物没有恢复自然杀伤细胞活性，并且更有可能死亡。当检查CY对淋巴细胞对B和T细胞有丝分裂原反应的影响时，未获得类似的相关性，治疗组之间在病理学上也没有显著差异。数据表明自然杀伤细胞在宿主抵御MCMV中起重要作用。此外，对MCMV易感性增加可能提供自然杀伤细胞反应缺陷的有用指标。
