{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:08:36Z","timestamp":1792188516388,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011720","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIGMS","award":["GM134880"],"award-info":[{"award-number":["GM134880"]}]},{"name":"NIH\/NIAID","award":["AI114543"],"award-info":[{"award-number":["AI114543"]}]},{"name":"NIH\/NIAID","award":["AI007485"],"award-info":[{"award-number":["AI007485"]}]},{"name":"NIH\/NIAID","award":["AI007511"],"award-info":[{"award-number":["AI007511"]}]},{"name":"NIH\/NIAID","award":["AI042767"],"award-info":[{"award-number":["AI042767"]}]},{"name":"NIH\/NIAID","award":["AI167847"],"award-info":[{"award-number":["AI167847"]}]},{"name":"NIH\/NIGMS","award":["GM140881"],"award-info":[{"award-number":["GM140881"]}]},{"name":"NCI","award":["CA086862"],"award-info":[{"award-number":["CA086862"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Sepsis, an amplified immune response to systemic infection, is characterized by a transient cytokine storm followed by chronic immune dysfunction. Consequently, sepsis survivors are highly susceptible to newly introduced infections, suggesting sepsis can influence the function and composition of the na\u00efve CD8 T cell pool and resulting pathogen-induced primary CD8 T cell responses. Here, we explored the extent to which sepsis induces phenotypic and functional changes within the na\u00efve CD8 T cell pool. To interrogate this, the cecal ligation and puncture (CLP) mouse model of polymicrobial sepsis was used. In normal, non-septic mice, we show type-I interferon (IFN I)-mediated signaling plays an important role in driving the phenotypic and functional heterogeneity in the na\u00efve CD8 T cell compartment leading to increased representation of Ly6C<jats:sup>+<\/jats:sup> na\u00efve CD8 T cells. In response to viral infection after sepsis resolution, na\u00efve Ly6C<jats:sup>+<\/jats:sup> CD8 T cells generated more primary effector and memory CD8 T cells with slower conversion to a central memory CD8 T cell phenotype (Tcm) than Ly6C<jats:sup>-<\/jats:sup> na\u00efve CD8 T cells. Importantly, as a potent inducer of cytokine storm and IFN I production, sepsis leads to increased representation of Ly6C<jats:sup>+<\/jats:sup> na\u00efve CD8 T cells that maintained their heightened ability to respond (i.e., effector and memory CD8 T cell accumulation and cytokine production) to primary LCMV infection. Lastly, longitudinal analyses of peripheral blood samples obtained from septic patients revealed profound changes in CD8 T cell subset composition and frequency compared to healthy controls. Thus, sepsis has the capacity to alter the composition of na\u00efve CD8 T cells, directly influencing primary CD8 T cell responses to newly introduced infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011720","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T17:46:50Z","timestamp":1697132810000},"page":"e1011720","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sepsis leads to lasting changes in phenotype and function of na\u00efve CD8 T cells"],"prefix":"10.1371","volume":"19","author":[{"given":"Roger R.","family":"Berton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W.","family":"McGonagil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac J.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany K.","family":"Ybarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail A.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Harty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-2439","authenticated-orcid":true,"given":"Vladimir P.","family":"Badovinac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"issue":"10219","key":"ppat.1011720.ref001","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study","volume":"395","author":"KE Rudd","year":"2020","journal-title":"Lancet"},{"key":"ppat.1011720.ref002","unstructured":"CDC. Sepsis: Technical resources & guidelines 2022, August 9. https:\/\/www.cdc.gov\/sepsis\/clinicaltools\/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fsepsis%2Fdatareports%2Findex.html."},{"issue":"3","key":"ppat.1011720.ref003","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S1473-3099(13)70001-X","article-title":"Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach","volume":"13","author":"S Richard","year":"2013","journal-title":"The Lancet Infectious Diseases"},{"issue":"9","key":"ppat.1011720.ref004","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1097\/CCM.0000000000001147","article-title":"Unplanned Readmissions After Hospitalization for Severe Sepsis at Academic Medical Center-Affiliated Hospitals","volume":"43","author":"JP Donnelly","year":"2015","journal-title":"Crit Care 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