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Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus

Abstract

Effective immunity is dependent on long-surviving memory T cells. Various memory subsets make distinct contributions to immune protection, especially in peripheral infection. It has been suggested that T cells in nonlymphoid tissues are important during local infection, although their relationship with populations in the circulation remains poorly defined. Here we describe a unique memory T cell subset present after acute infection with herpes simplex virus that remained resident in the skin and in latently infected sensory ganglia. These T cells were in disequilibrium with the circulating lymphocyte pool and controlled new infection with this virus. Thus, these cells represent an example of tissue-resident memory T cells that can provide protective immunity at points of pathogen entry.

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Figure 1: Tissue-resident memory T cells fail to recirculate after localized or systemic viral infection.
Figure 2: Long-term retention of virus-specific CD8+ T cells at the site of previous viral infection.
Figure 3: HSV-specific CD8+ T cells 'preferentially' localize to the epidermal skin layer covering the previously infected site and express the intraepithelial cell marker CD103.
Figure 4: Skin-resident, virus-specific CD8+ T cells are phenotypically and functionally different from their circulating counterparts.
Figure 5: Skin-resident, virus-specific T cells persist in situ after transplantation of previously infected skin onto naive recipients.
Figure 6: Local virus-specific T cells contribute to protection against reinfection with HSV.

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Acknowledgements

We thank S. Tevethia (Pennsylvania State University) for WSN/NA/gB; P. Doherty (The University of Melbourne) for WSN/NA/OVA; J. Yewdell (U.S. National Institutes of Health) for vaccinia-NP.; D. Masopust for discussions; and H. Kosaka for suggesting that fixed drug eruptions are caused by resident T cells. Supported by the Australian National Health and Medical Research Council, the Howard Hughes Medical Institute and the German Research Foundation (GE1666/1-1 to T.G.).

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Correspondence to William R Heath or Francis R Carbone.

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Gebhardt, T., Wakim, L., Eidsmo, L. et al. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol 10, 524–530 (2009). https://doi.org/10.1038/ni.1718

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