Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation

J Zhu, DM Koelle, J Cao, J Vazquez… - The Journal of …, 2007 - rupress.org
J Zhu, DM Koelle, J Cao, J Vazquez, ML Huang, F Hladik, A Wald, L Corey
The Journal of experimental medicine, 2007rupress.org
Cytotoxic CD8+ T cells play a critical role in controlling herpes simplex virus (HSV) infection
and reactivation. However, little is known about the spatiotemporal dynamics of CD8+ T cells
during HSV lesion evolution or about their involvement in immune surveillance after lesion
resolution. Using quantum dot–conjugated peptide–major histocompatibility complex
multimers, we investigated the in vivo localization of HSV-2–specific CD8+ T cells in
sequential biopsies of human genital skin during acute, resolving, and healed stages of HSV …
Cytotoxic CD8+ T cells play a critical role in controlling herpes simplex virus (HSV) infection and reactivation. However, little is known about the spatiotemporal dynamics of CD8+ T cells during HSV lesion evolution or about their involvement in immune surveillance after lesion resolution. Using quantum dot–conjugated peptide–major histocompatibility complex multimers, we investigated the in vivo localization of HSV-2–specific CD8+ T cells in sequential biopsies of human genital skin during acute, resolving, and healed stages of HSV-2 reactivation. Our studies revealed that functionally active CD8+ T cells selectively infiltrated to the site of viral reactivation. After lesion healing in concert with complete reepithelialization and loss of HSV DNA from skin biopsies, HSV-2–specific CD8+ T cells persisted for more than two months at the dermal–epidermal junction, adjacent to peripheral nerve endings. In two out of the six sequentially studied individuals, HSV-2 DNA reappeared in clinically and histologically normal–appearing skin. Detection of viral DNA was accompanied by increased numbers of both HSV-specific and total CD8+ T cells in the dermis. These findings indicate that the frequency and clinical course of HSV-2 reactivation in humans is influenced by virus-specific CD8+ T cells that persist in peripheral mucosa and genital skin after resolution of herpes lesions.
rupress.org