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Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection.
Title | Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Zhu, J, Peng, T, Johnston, C, Phasouk, K, Kask, AS, Klock, A, Jin, L, Diem, K, Koelle, DM, Wald, A, Robins, H, Corey, L |
Journal | Nature |
Volume | 497 |
Issue | 7450 |
Pagination | 494-7 |
Date Published | 2013 May 23 |
ISSN | 1476-4687 |
Keywords | Adult, CD8-Positive T-Lymphocytes, Clone Cells, Herpes Genitalis, Herpesvirus 2, Human, Humans, Immunologic Memory, Immunologic Surveillance, Receptors, Antigen, T-Cell, alpha-beta, Skin |
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. |
DOI | 10.1038/nature12110 |
Alternate Journal | Nature |
PubMed ID | 23657257 |