Resident memory CD8 T cells trigger protective innate and adaptive immune responses

By J. Schenkel, Kathryn A. Fraser, Lalit K. Beura, Kristen E. Pauken, V. Vezys, D. Masopust. Science, 2014

634 citations recorded by the source corpus.

Resident memory T cells sound the alarm Immunological memory protects against reinfection. Resident memory T cells (TRM) are long-lived and remain in the tissues where they first encountered a pathogen (see the Perspective by Carbone and Gebhardt). Schenkel et al. and Ariotti et al. found that CD8+ TRM cells act like first responders in the female reproductive tissue or the skin of mice upon antigen reencounter. By secreting inflammatory proteins, TRM cells rapidly activated local immune cells to respond, so much so that they protected against infection with an unrelated pathogen. Iijima and Iwasaki found that CD4+ TRM cells protected mice against reinfection with intravaginal herpes simplex virus 2. Science, this issue p. 98, p. 101, p. 93; see also p. 40 Resident memory CD8+ T cells orchestrate a broad immune response in response to reinfection. [Also see Perspective by Carbone and Gebhardt] The pathogen recognition theory dictates that, upon viral infection, the innate immune system first detects microbial products and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that tissue resident memory CD8 T cells (TRM cells), non-recirculating cells located at common sites of infection, can achieve near-sterilizing immunity against viral infections by reversing this flow of information. Upon antigen resensitization within the mouse female reproductive mucosae, CD8+ TRM cells secrete cytokines that trigger rapid adaptive and innate immune responses, including local humoral responses, maturation of local dendritic cells, and activation of natural killer cells. This provided near-sterilizing immunity against an antigenically unrelated viral infection. Thus, CD8+ TRM cells rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/5700ad4b724404f69a6c981c72dbee3aa12eeaf5

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In Immunology

1. J. Schenkel
2. D. Masopust
3. D. Farber
4. Brahma V. Kumar
5. Y. Bryceson

Citations in the corpus

• Tissue-Resident Memory T Cells (2014, background): “Parabiosis experiments demonstrated that 1%–5% of memory CD8+ T cells within spleen and LNs are Trm cells after acute LCMV infection (Schenkel et al., 2014a).”
• Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites (2017, background): “While TRMs have been detected in mouse lymph nodes (Schenkel et al., 2014b; Ugur et al., 2014), the majority of mouse lymphoid memory CD4+ and CD8+ T cells in mice are circulating, particularly those in the spleen.”
• Human T cell development, localization, and function throughout life (2018, background): “…viral, bacterial, and parasite infections, and are more effective than circulating memory T cells in pathogen clearance (Fernandez-Ruiz et al., 2016; Gebhardt et al., 2009; Glennie et al., 2015; Jiang et al., 2012; Sakai et al., 2014; Schenkel et al., 2014; Teijaro et al., 2011; Thom et al., 2015).”
• Cellular and molecular mechanisms of skin wound healing (2024, neutral): “Upon activation, TRM cells act by directly killing virally infected cells 194 and by inducing a generalized antiviral state in the skin, promoting the release of IFNγ by keratinocytes 195,196 .”
• CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin (2017, positive): “In line with our study of human skin, granzyme B-expressing Trm cells are retained in mouse epithelium following epidermo- tropic viral infections (Gebhardt et al., 2009; Schenkel et al., 2014).”