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- Title
In Situ Detection of Regulatory T Cells in Human Genital Herpes Simplex Virus Type 2 (HSV-2) Reactivation and Their Influence on Spontaneous HSV-2 Reactivation.
- Authors
Milman, Neta; Jia Zhu; Johnston, Christine; Anqi Cheng; Magaret, Amalia; Koelle, David M.; Meei-Li Huang; Lei Jin; Klock, Alexis; Layton, Erik D.; Corey, Lawrence; Zhu, Jia; Cheng, Anqi; Huang, Meei-Li; Jin, Lei
- Abstract
<bold>Background: </bold>Herpes simplex virus type 2 (HSV-2) reactivation is accompanied by a sustained influx of CD4(+) and CD8(+) T cells that persist in genital tissue for extended periods. While CD4(+) T cells have long been recognized as being present in herpetic ulcerations, their role in subclinical reactivation and persistence is less well known, especially the role of CD4(+) regulatory T cells (Tregs).<bold>Methods: </bold>We characterized the Treg (CD4(+)Foxp3(+)) population during human HSV-2 reactivation in situ in sequential genital skin biopsy specimens obtained from HSV-2-seropositive subjects at the time of lesion onset up to 8 weeks after healing.<bold>Results: </bold>High numbers of Tregs infiltrated to the site of viral reactivation and persisted in proximity to conventional CD4(+) T cells (Tconvs) and CD8(+) T cells. Treg density peaked during the lesion stage of the reactivation. The number of Tregs from all time points (lesion, healed, 2 weeks after healing, 4 weeks after healing, and 8 weeks after healing) was significantly higher than in control biopsy specimens from unaffected skin. There was a direct correlation between HSV-2 titer and Treg density.<bold>Conclusions: </bold>The association of a high Treg to Tconv ratio with high viral shedding suggests that the balance between regulatory and effector T cells influences human HSV-2 disease.
- Subjects
WASHINGTON (State); HERPES simplex virus; T cells; ULCERS; IMMUNITY; IMMUNOLOGY; HERPESVIRUSES; GENITALIA; HERPES genitalis; RESEARCH funding; VIRAL physiology; PHYSIOLOGY
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 1, p23
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw091