Latent Cytomegalovirus (CMV) Infection Does Not Detrimentally Alter T Cell Responses in the Healthy Old, But Increased Latent CMV Carriage Is Related to Expanded CMV-Specific T Cells.
Latent Cytomegalovirus (CMV) Infection Does Not Detrimentally Alter T Cell Responses in the Healthy Old, But Increased Latent CMV Carriage Is Related to Expanded CMV-Specific T Cells.
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DOI：
10.3389/fimmu.2017.00733
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发表时间：
2017
影响因子：
7.3
通讯作者：
Wills MR
中科院分区：
文献类型：
--
作者：
Jackson SE;Sedikides GX;Okecha G;Poole EL;Sinclair JH;Wills MR
人巨细胞病毒（HCMV）的原发性感染和潜伏病毒的周期性再激活通常可以通过健康人的T细胞反应得到很好的控制。在老年供体中，尽管HCMV感染与死亡风险增加相关，但通常不会观察到明显的HCMV疾病。然而，老年人尿液中HCMV DNA的增加表明，尽管免疫应答保留了功能，但由于终身病毒携带引起的免疫应答的免疫调节可能会改变其疗效。病毒转录在潜伏期期间限于少数病毒基因，并且存在IFNγ和细胞IL-10 CD 4 + T细胞对HCMV潜伏相关蛋白的应答。由HCMV特异性CD 4 + T细胞产生cIL-10是衰老相关免疫调节的候选者。为了研究HCMV的长期携带是否改变了分泌cIL-10和IFNγ的T细胞群的平衡，我们招募了一个年龄在23-78岁之间的大型供体队列，并将T细胞对11种HCMV蛋白的应答与年龄、HCMV IgG水平、CD 14+单核细胞中的潜伏HCMV载量和血液中的T细胞数量相关联。检测到CD 4+和CD 8 + T细胞对所有HCMV蛋白的IFNγ应答，在该队列中没有年龄相关的增加。IL-10分泌的CD 4 + T细胞反应主要是潜伏相关蛋白，但不随年龄增加。在CD 14+单核细胞（一个已知的潜伏性HCMV携带位点）中，HCMV基因组的定量没有显示老年供体中病毒基因组拷贝的任何增加。重要的是，潜伏病毒基因组拷贝数与IFNγ T细胞对HCMV蛋白应答的广度和幅度之间存在显著正相关。这项研究表明，在健康的老年供体中，T细胞区室中的HCMV特异性变化不受年龄的影响，并且是有效的，因为病毒血症是非常罕见的事件。来自不健康老年人的研究证据表明HCMV是一个重要的合并症因素，监测血液和体液中的潜伏HCMV载量和低水平病毒血症，以及典型的免疫学措施和评估HCMV特异性免疫细胞功能的抗病毒能力，将在确定老年人HCMV复制的抗病毒治疗是否有益时提供信息。
Human cytomegalovirus (HCMV) primary infection and periodic reactivation of latent virus is generally well controlled by T-cell responses in healthy people. In older donors, overt HCMV disease is not generally seen despite the association of HCMV infection with increased risk of mortality. However, increases in HCMV DNA in urine of older people suggest that, although the immune response retains functionality, immunomodulation of the immune response due to lifelong viral carriage may alter its efficacy. Viral transcription is limited during latency to a handful of viral genes and there is both an IFNγ and cellular IL-10 CD4+ T-cell response to HCMV latency-associated proteins. Production of cIL-10 by HCMV-specific CD4+ T-cells is a candidate for aging-related immunomodulation. To address whether long-term carriage of HCMV changes the balance of cIL-10 and IFNγ-secreting T-cell populations, we recruited a large donor cohort aged 23–78 years and correlated T-cell responses to 11 HCMV proteins with age, HCMV IgG levels, latent HCMV load in CD14+ monocytes, and T-cell numbers in the blood. IFNγ responses by CD4+ and CD8+ T-cells to all HCMV proteins were detected, with no age-related increase in this cohort. IL-10-secreting CD4+ T cell responses were predominant to latency-associated proteins but did not increase with age. Quantification of HCMV genomes in CD14+ monocytes, a known site of latent HCMV carriage, did not reveal any increase in viral genome copies in older donors. Importantly, there was a significant positive correlation between the latent viral genome copy number and the breadth and magnitude of the IFNγ T-cell response to HCMV proteins. This study suggests in healthy aged donors that HCMV-specific changes in the T cell compartment were not affected by age and were effective, as viremia was a very rare event. Evidence from studies of unwell aged has shown HCMV to be an important comorbidity factor, surveillance of latent HCMV load and low-level viremia in blood and body fluids, alongside typical immunological measures and assessment of the antiviral capacity of the HCMV-specific immune cell function would be informative in determining if antiviral treatment of HCMV replication in the old maybe beneficial.