Department of Medicine, University of Washington, Seattle, Washington, USA.
J Virol. 2012 Oct;86(19):10587-96. doi: 10.1128/JVI.01237-12. Epub 2012 Jul 18.
Herpes simplex virus 2 infection is characterized by cycles of viral quiescence and reactivation. CD8(+) T cells persist at the site of viral reactivation, at the genital dermal-epidermal junction contiguous to neuronal endings of sensory neurons, for several months after herpes lesion resolution. To evaluate whether these resident CD8(+) T cells frequently encounter HSV antigen even during times of asymptomatic viral infection, we analyzed the transcriptional output of CD8(+) T cells captured by laser microdissection from human genital skin biopsy specimens during the clinically quiescent period of 8 weeks after lesion resolution. These CD8(+) T cells expressed a characteristic set of genes distinct from those of three separate control cell populations, and network and pathway analyses revealed that these T cells significantly upregulated antiviral genes such as GZMB, PRF1, INFG, IL-32, and LTA, carbohydrate and lipid metabolism-related genes such as GLUT-1, and chemotaxis and recruitment genes such as CCL5 and CCR1, suggesting a possible feedback mechanism for the recruitment of CD8(+) T cells to the site of infection. Many of these transcripts are known to have half-lives of <48 h, suggesting that cognate antigen is released frequently into the mucosa and that resident CD8(+) T cells act as functional effectors in controlling viral spread.
单纯疱疹病毒 2 感染的特征是病毒静止和再激活的循环。在疱疹病变消退后几个月内，CD8(+) T 细胞持续存在于病毒再激活部位，即生殖器真皮-表皮交界处，与感觉神经元的神经元末梢相邻。为了评估这些常驻 CD8(+) T 细胞即使在无症状病毒感染期间是否经常遇到 HSV 抗原，我们分析了从疱疹病变消退后 8 周临床无症状感染期间的人生殖器皮肤活检标本中通过激光微切割捕获的 CD8(+) T 细胞的转录输出。这些 CD8(+) T 细胞表达了一组与三个单独的对照细胞群明显不同的特征性基因，网络和途径分析表明，这些 T 细胞显著上调了抗病毒基因，如 GZMB、PRF1、INFG、IL-32 和 LTA，以及碳水化合物和脂质代谢相关基因，如 GLUT-1，以及趋化和招募基因，如 CCL5 和 CCR1，这表明 CD8(+) T 细胞可能存在一种募集到感染部位的反馈机制。这些转录物中有许多已知的半衰期<48 h，这表明同源抗原经常被释放到黏膜中，并且常驻 CD8(+) T 细胞作为控制病毒传播的功能性效应物发挥作用。
