Stowe Raymond P, Kozlova Elena V, Yetman Deborah L, Walling Dennis M, Goodwin James S, Glaser Ronald
Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States.
Exp Gerontol. 2007 Jun;42(6):563-70. doi: 10.1016/j.exger.2007.01.005. Epub 2007 Jan 30.
The aged immune system is characterized by clonal expansions of CD8+ T cells of which a substantial portion are directed against Epstein-Barr virus (EBV) and cytomegalovirus (CMV). It is unknown if these expansions represent increased viral reactivation or simply reflect an accumulation over time. We investigated herpesvirus reactivation in young and old subjects co-infected with CMV and EBV. Using molecular and serological techniques, we found significant increases in both the frequency and magnitude of EBV and CMV reactivation in elderly subjects. CMV DNA was frequently detected in the urine of elderly subjects; EBV load in peripheral blood was also significantly increased. Notably, EBV DNA in plasma was detected in a majority of the elderly subjects which was supported by frequent transcription of late structural genes. Furthermore, CD8+ T cells specific for EBV structural antigens were detected in samples from the elderly. Samples from our younger control group were negative for EBV DNA in plasma, CMV DNA in urine, expression of structural transcripts, and lacked CD8+ T cells specific for EBV structural antigens. These findings indicate that the aged immune system is no longer able to control EBV and CMV reactivation that could now be characterized as chronic instead of latent.
衰老的免疫系统的特征是CD8+ T细胞的克隆性扩增，其中很大一部分针对爱泼斯坦-巴尔病毒（EBV）和巨细胞病毒（CMV）。目前尚不清楚这些扩增是代表病毒再激活增加还是仅仅反映了随时间的积累。我们研究了同时感染CMV和EBV的年轻和老年受试者中的疱疹病毒再激活情况。使用分子和血清学技术，我们发现老年受试者中EBV和CMV再激活的频率和幅度均显著增加。在老年受试者的尿液中经常检测到CMV DNA；外周血中的EBV载量也显著增加。值得注意的是，大多数老年受试者的血浆中检测到EBV DNA，这得到了晚期结构基因频繁转录的支持。此外，在老年受试者的样本中检测到了针对EBV结构抗原的CD8+ T细胞。我们年轻对照组的样本在血浆中的EBV DNA、尿液中的CMV DNA、结构转录本的表达方面均为阴性，并且缺乏针对EBV结构抗原的CD8+ T细胞。这些发现表明，衰老的免疫系统不再能够控制EBV和CMV的再激活，现在可以将其表征为慢性而非潜伏性。
