The Journal of Experimental Medicine
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Published online February 26, 2007
doi:10.1084/jem.20061792
The Journal of Experimental Medicine, Vol. 204, No. 3, 595-603
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Zhu et al.
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ARTICLE

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

Jia Zhu1,6, David M. Koelle1,2,4,6,9, Jianhong Cao7, Julio Vazquez8, Meei Li Huang1,6, Florian Hladik2,5,6, Anna Wald1,2,3,6, and Lawrence Corey1,2,4,6

1 Department of Laboratory Medicine, 2 Department of Medicine, 3 Department of Epidemiology, 4 Department of Pathobiology, and 5 Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195
6 Infectious Diseases Program, 7 Immune Monitoring Lab, and 8 Scientific Imaging, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
9 Benaroya Research Institute, Seattle, WA 98104

CORRESPONDENCE Lawrence Corey: lcorey{at}u.washington.edu

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.

Abbreviations used: NCAM, neural cell adhesion molecule; Qdot, quantum dot; Qdot multimer, Qdot-conjugated peptide–MHC multimer.


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