title: Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection.
abstract: Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown that CD8(+) T cells persist in genital skin and mucosa at the dermal-epidermal junction (DEJ)--the portal of neuronal release of reactivating virus--for prolonged time periods after herpes lesions are cleared. The phenotype and function of this persistent CD8(+) T-cell population remain unknown. Here, using cell-type-specific laser capture microdissection, transcriptional profiling and T-cell antigen receptor β-chain (TCRβ) genotyping on sequential genital skin biopsies, we show that CD8αα(+) T cells are the dominant resident population of DEJ CD8(+) T cells that persist at the site of previous HSV-2 reactivation. CD8αα(+) T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. Sequencing of the TCR β-chain repertoire reveals that the DEJ CD8αα(+) T cells are oligoclonal with diverse usage of TCR variable-β genes, which differ from those commonly described for mucosa-associated invariant T cells and natural killer T cells. Dominant clonotypes are shown to overlap among multiple recurrences over a period of two-and-a-half years. Episodes of rapid asymptomatic HSV-2 containment were also associated with a high CD8 effector-to-target ratio and focal enrichment of CD8αα(+) T cells. These studies indicate that DEJ CD8αα(+) T cells are tissue-resident cells that seem to have a fundamental role in immune surveillance and in initial containment of HSV-2 reactivation in human peripheral tissue. Elicitation of CD8αα(+) T cells may be a critical component for developing effective vaccines against skin and mucosal infections.
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA. jiazhu@u.washington.edu
authors: Jia
authors: J
authors: Zhu
authors: Tao
authors: T
authors: Peng
authors: Christine
authors: C
authors: Johnston
authors: Khamsone
authors: K
authors: Phasouk
authors: Angela S
authors: AS
authors: Kask
authors: Alexis
authors: A
authors: Klock
authors: Lei
authors: L
authors: Jin
authors: Kurt
authors: K
authors: Diem
authors: David M
authors: DM
authors: Koelle
authors: Anna
authors: A
authors: Wald
authors: Harlan
authors: H
authors: Robins
authors: Lawrence
authors: L
authors: Corey
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007157:Immunologic Surveillance; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta
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