Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity

By Xiaodong Jiang, R. Clark, Luzheng Liu, A. Wagers, R. Fuhlbrigge, T. Kupper. Nature, 2012

863 citations recorded by the source corpus.

Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (TRM) cells has been proposed. Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8+ skin TRM cells that reside within the entire skin. These skin TRM cells are potent effector cells, and are superior to circulating central memory T (TCM) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8+ T cells are rapidly recruited to skin after acute VACV infection. CD8+ T-cell recruitment to skin is independent of CD4+ T cells and interferon-γ, but requires the expression of E- and P-selectin ligands by CD8+ T cells. Using parabiotic mice, we further show that circulating CD8+ TCM and CD8+ skin TRM cells are both generated after skin infection; however, CD8+ TCM cells recirculate between blood and lymph nodes whereas TRM cells remain in the skin. Cutaneous CD8+ TRM cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8+ skin TRM cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating TCM but no skin TRM cells showed greatly impaired viral clearance, indicating that TRM cells provide superior protection. Finally, we show that TRM cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective TRM cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/c198419367463b4d0e75005ef6e0d71d3e01b2b8

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Citations in the corpus

Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells (2013, neutral): “…are virusspecific cells that persist in the mucosae and skin after the resolution of viral infections (Casey et al., 2012; Gebhardt et al., 2009; Jiang et al., 2012; Sathaliyawala et al., 2013; Wakim Immunity 38, 1–13, April 18, 2013 ª2013 Elsevier Inc. 1 (legend continued on next page) Type 1…”
Human T cell development, localization, and function throughout life (2018, background): “…in diverse types of tissues including barrier sites, mucosal tissues, liver, salivary glands, and brain, where they are retained and do not recirculate as shown by parabiosis and in vivo labeling studies (Jiang et al., 2012; Mueller and Mackay, 2016; Steinert et al., 2015; Teijaro et al., 2011).”
Quantifying memory CD8 T cells reveals regionalization of immunosurveillance (2015, background): “These observations revise perceptions of immunosurveillance and may help explain why frontline memory CD8 T cell populations can rapidly detect infections in barrier tissues (Gebhardt et al., 2009; Jiang et al., 2012; Shin and Iwasaki, 2012; Teijaro et al., 2011; Wu et al., 2014).”
Tissue-Resident Memory T Cells (2014, background): “Shorter-term studies in mice and rhesus macaques revealed that tissue memory CD8+ T cells are relatively stable for 300–700 days (Jiang et al., 2012; Kaufman et al., 2008; Masopust et al., 2001b).”
Chemokines and chemokine receptors: positioning cells for host defense and immunity. (2014, background): “In any case, TRM appear uniquely positioned in the peripheral tissue to quickly enact effector functions and provide protection from reinfection or reactivation of latent virus (214, 215).”
Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites (2017, background): “In mice, tissue retention demonstrated by parabiosis (Jiang et al., 2012; Steinert et al., 2015) and in vivo antibody labeling (Anderson et al., 2014; Turner et al., 2014) identified phenotypic markers associated with tissue residence, including CD69 and CD103.”
CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin (2017, positive): “While such local immune responses contribute to immunity (Gebhardt et al., 2009; Glennie et al., 2015; Jiang et al., 2012; Naik et al., 2012), aberrant activation might cause disease (Hondowicz et al.”