Recurrent infection transiently expands human tissue T cells while maintaining long-term homeostasis

The immune cell compartment in human genital skin expands and contracts following HSV-2 reactivation, and includes cells recruited from circulation and proliferating cells. Despite frequent antigen exposure, tissue T cell number and phenotype remain stable in the long-term, likely driven at least in part by cell-extrinsic and cell-intrinsic regulatory mechanisms. 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.

Automated summary

The immune cell compartment in genital skin expands and contracts following HSV-2 reactivation, and includes cells recruited from circulation and proliferating cells. Despite frequent antigen exposure, tissue T cell number and phenotype remain stable in the long-term, likely driven by regulatory mechanisms. It remains unclear if periodic viral reactivation can induce T cell dysfunction in a localized infection.