Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Global Health, Graduate Program in Pathobiology, University of Washington, Seattle, WA, USA.
J Exp Med. 2023 Sep 4;220(9). doi: 10.1084/jem.20210692. Epub 2023 Jun 14.
Chronic viral infections are known to lead to T cell exhaustion or dysfunction. However, it remains unclear if antigen exposure episodes from periodic viral reactivation, such as herpes simplex virus type-2 (HSV-2) recrudescence, are sufficient to induce T cell dysfunction, particularly in the context of a tissue-specific localized, rather than a systemic, infection. We designed and implemented a stringent clinical surveillance protocol to longitudinally track both viral shedding and in situ tissue immune responses in a cohort of HSV+ volunteers that agreed to avoid using anti-viral therapy for the course of this study. Comparing lesion to control skin biopsies, we found that tissue T cells expanded immediately after reactivation, and then returned numerically and phenotypically to steady state. T cell responses appeared to be driven at least in part by migration of circulating T cells to the infected tissue. Our data indicate that tissue T cells are stably maintained in response to HSV reactivation, resembling a series of acute recall responses.
慢性病毒感染已知会导致 T 细胞衰竭或功能障碍。然而，目前尚不清楚周期性病毒再激活（如单纯疱疹病毒 2 型[HSV-2]复发）引起的抗原暴露事件是否足以诱导 T 细胞功能障碍，特别是在组织特异性局部感染而不是全身性感染的情况下。我们设计并实施了一项严格的临床监测方案，以纵向跟踪一组同意在本研究过程中避免使用抗病毒治疗的 HSV+志愿者的病毒脱落和原位组织免疫反应。通过比较病变和对照皮肤活检，我们发现组织 T 细胞在再激活后立即扩增，然后在数量和表型上恢复到稳定状态。T 细胞反应似乎至少部分是由循环 T 细胞向感染组织的迁移驱动的。我们的数据表明，组织 T 细胞在 HSV 再激活时稳定维持，类似于一系列急性回忆反应。
