Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation.
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.
Zhu
Jia
J
Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
Koelle
David M
DM
Cao
Jianhong
J
Vazquez
Julio
J
Huang
Meei Li
ML
Hladik
Florian
F
Wald
Anna
A
Corey
Lawrence
L
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000294:innervation; D005837:Genitalia, Male / Q000294:innervation; D006558:Herpes Genitalis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009411:Nerve Endings / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017193:Skin Diseases, Viral / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014775:Virus Activation / Q000276:immunology*