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Interestingly, the relative susceptibility of memory CD8 T cell subsets to quantitative\/qualitative changes differ after cecal ligation and puncture (CLP)\u2013induced sepsis. Compared with circulatory memory CD8 T cells (TCIRCM), moderate sepsis (0\u201310% mortality) does not result in numerical decline of CD8 tissue-resident memory T cells (TRM), which retain their \u201csensing and alarm\u201d IFN-\u03b3\u2013mediated effector function. To interrogate this biologically important dichotomy, vaccinia virus\u2013immune C57BL\/6 (B6) mice containing CD8 TCIRCM and skin TRM underwent moderate or severe (\u223c50% mortality) sepsis. Severe sepsis led to increased morbidity and mortality characterized by increased inflammation compared with moderate CLP or sham controls. Severe CLP mice also displayed increased vascular permeability in the ears. Interestingly, skin CD103+ CD8 TRM, detected by i.v. exclusion or two-photon microscopy, underwent apoptosis and subsequent numerical loss following severe sepsis, which was not observed in mice that experienced moderate CLP or sham surgeries. Consequently, severe septic mice showed diminished CD8 T cell\u2013mediated protection to localized skin reinfection. Finally, the relationship between severity of sepsis and demise in circulatory versus tissue-embedded memory CD8 T cell populations was confirmed by examining tumor-infiltrating and nonspecific CD8 T cells in B16 melanoma tumors. Thus, sepsis can differentially affect the presence and function of Ag-specific CD8 T cells that reside inside tissues\/tumors depending on the severity of the insult, a notion with direct relevance to sepsis survivors and their ability to mount protective memory CD8 T cell\u2013dependent responses to localized Ag re-encounter.<\/jats:p>","DOI":"10.4049\/jimmunol.2001142","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T18:25:50Z","timestamp":1630693550000},"page":"1871-1881","source":"Crossref","is-referenced-by-count":17,"title":["Severity of Sepsis Determines the Degree of Impairment Observed in Circulatory and Tissue-Resident Memory CD8 T Cell Populations"],"prefix":"10.1093","volume":"207","author":[{"given":"Steven J","family":"Moioffer","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek B","family":"Danahy","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"},{"name":"Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"van de Wall","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-3961","authenticated-orcid":false,"given":"Isaac J","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"},{"name":"Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances V","family":"Sjaastad","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-7401","authenticated-orcid":false,"given":"Scott M","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7266-2802","authenticated-orcid":false,"given":"John T","family":"Harty","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"},{"name":"Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-9859","authenticated-orcid":false,"given":"Thomas S","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Minnesota , Minneapolis, MN"},{"name":"Minneapolis Veterans Affairs Health Care System , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-2439","authenticated-orcid":false,"given":"Vladimir P","family":"Badovinac","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA"},{"name":"Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA"},{"name":"Department of Microbiology and Immunology, University of Iowa , Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"2025022610321603700_r1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMra021333","article-title":"The pathophysiology and treatment of sepsis","volume":"348","author":"Hotchkiss","year":"2003","journal-title":"N. 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