1. 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.
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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, and Jin, Lei
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HERPES simplex virus , *T cells , *ULCERS , *IMMUNITY , *IMMUNOLOGY , *HERPESVIRUSES , *GENITALIA , *HERPES genitalis , *RESEARCH funding , *VIRAL physiology , *PHYSIOLOGY - Abstract
Background: 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).Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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