Tyler B Rollman, Zachary W Berkebile, Dustin M Hicks, Jason S Hatfield, Priyanka Chauhan, Marco Pravetoni, Mark R Schleiss, Gregg N Milligan, Terry K Morgan, Craig J Bierle
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引用次数: 0
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious disease related birth defects worldwide. How the immune response modulates the risk of intrauterine transmission of HCMV after maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread across the placenta, but concerns exist that immune responses to infection may also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4+ and CD8+ T cells in a guinea pig model of primary cytomegalovirus infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non-pregnant and in pregnant guinea pigs after mid-gestation. CD4+ T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital guinea pig cytomegalovirus (GPCMV) infection relative to animals treated with control antibody. CD8+ T cell depletion was comparably well tolerated and did not significantly affect the weight of infected guinea pigs or viral loads in their blood or tissue. However, significantly more viral genomes and transcripts were detected in the placenta and decidua of CD8+ T cell depleted dams post-infection. This study corroborates earlier findings made in nonhuman primates that maternal CD4+ T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also revealing that other innate and adaptive immune responses can compensate for an absent CD8+ T cell response in α-CD8-treated guinea pigs.
人类巨细胞病毒(HCMV)是一种无处不在的疱疹病毒,也是导致全球与传染病相关的出生缺陷的主要原因。人们对母体感染后免疫反应如何调节 HCMV 宫内传播风险仍知之甚少。母体 T 细胞在防止母胎界面感染和限制胎盘传播方面可能起着关键作用,但人们担心,对感染的免疫反应也可能导致胎盘功能障碍和不良妊娠结局。本研究调查了 CD4+ 和 CD8+ T 细胞在豚鼠原发性巨细胞病毒感染模型中的作用。在妊娠中期后,使用豚鼠 CD4 和 CD8 特异性单克隆抗体消耗非妊娠豚鼠和妊娠豚鼠的 T 细胞。与使用对照抗体的动物相比,CD4+ T细胞耗竭会增加疾病的严重程度,导致病毒载量显著升高,并增加先天性豚鼠巨细胞病毒(GPCMV)感染率。CD8+ T 细胞耗竭的耐受性相当好,对受感染豚鼠的体重或其血液或组织中的病毒载量没有显著影响。然而,在感染后CD8+ T细胞耗竭的母鼠胎盘和蜕膜中检测到的病毒基因组和转录本明显增多。这项研究证实了早先在非人灵长类动物身上的发现,即母体 CD4+ T 细胞在限制妊娠期原发性 CMV 感染的严重程度方面起着至关重要的作用,同时也揭示了其他先天性和适应性免疫反应可以补偿经 α-CD8 处理的豚鼠体内 CD8+ T 细胞反应的缺失。
期刊介绍:
Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.