{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T21:29:52Z","timestamp":1775510992366,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["Ciencia B\u00e1sica 2015-256752"],"award-info":[{"award-number":["Ciencia B\u00e1sica 2015-256752"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sepsis is a complex condition of inflammatory and immune dysregulation, triggered by severe infection. In survivors, chronic inflammation and immune dysregulation linger, facilitating the emergence of infections. CD8 dysfunction contributes to immunosuppression in sepsis survivors. We devised an animal model that enabled us to identify and analyze CD8-intrinsic defects induced by sepsis. We adoptively transferred CD45.1 CD8 OT-I T cells into CD45.2 congenic mice and subjected them to cecal ligature and puncture, to induce abdominal sepsis. One month later, we isolated the transferred CD8 cells. Surface marker expression confirmed they had not been activated through the TCR. CD8 OT-I T cells isolated from septic (or sham-operated) mice were transferred to second recipients, which were challenged with OVA-expressing Listeria monocytogenes. We compared effector capacities between OT-I cells exposed to sepsis and control cells. Naive mice that received OT-I cells exposed to sepsis had higher bacterial burden and a shorter survival when challenged with OVA-expressing L. monocytogenes. OT-I cells isolated from septic mice produced less IFN-\u03b3 but had conserved activation, expansion potential, and cytotoxic function. We observed lower transcript levels of IFN-\u03b3 and of the long noncoding RNA Ifng-as1, a local regulator of the epigenetic landscape, in cells exposed to sepsis. Accordingly, local abundance of a histone modification characteristic of active promoter regions was reduced in sepsis-exposed CD8 T cells. Our results identify a mechanism through which inflammation in the context of sepsis affects CD8 T cell function intrinsically.<\/jats:p>","DOI":"10.4049\/jimmunol.2300772","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T12:58:02Z","timestamp":1721653082000},"page":"619-627","source":"Crossref","is-referenced-by-count":3,"title":["Sepsis Impairs IFN-\u03b3 Production in CD8 T Cells through Changes in Local Chromatin Landscape"],"prefix":"10.1093","volume":"213","author":[{"given":"J Alejandro","family":"Cisneros-Segura","sequence":"first","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]},{"name":"Programa de Maestr\u00eda y Doctorado en Ciencias Bioqu\u00edmicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00e9","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]},{"name":"Medical Research Council, Laboratory of Molecular Biology , Cambridge ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adri\u00e1n","family":"Albarr\u00e1n-God\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]},{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Benjam\u00edn","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos A","family":"Rodr\u00edguez-Osorio","sequence":"additional","affiliation":[{"name":"Departament of Critical Care, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]},{"name":"Respiratory Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias \u201cIsmael Cos\u00edo Villegas,\u201d \u00a0 Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio Iv\u00e1n","family":"Vald\u00e9s-Ferrer","sequence":"additional","affiliation":[{"name":"Department of Neurology & Psychiatry, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]},{"name":"Center for Biomedical Science, Feinstein Institutes for Medical Research , New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9246-7445","authenticated-orcid":false,"given":"Gustavo","family":"Tapia-Urz\u00faa","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Departamento de Gen\u00e9tica Molecular, Universidad Nacional Aut\u00f3noma de M\u00e9xico , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-0407","authenticated-orcid":false,"given":"F\u00e9lix","family":"Recillas-Targa","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Departamento de Gen\u00e9tica Molecular, Universidad Nacional Aut\u00f3noma de M\u00e9xico , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris K","family":"Madera-Salcedo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-4515","authenticated-orcid":false,"given":"Florencia","family":"Rosetti","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-3621","authenticated-orcid":false,"given":"Jos\u00e9 C","family":"Crisp\u00edn","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , Mexico City ,","place":["Mexico"]},{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey , Mexico City ,","place":["Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"2025012305140954200_r1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"2025012305140954200_r2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S2213-2600(14)70061-X","article-title":"Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit","volume":"2","author":"Vincent","year":"2014","journal-title":"Lancet Respir. 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Res."},{"key":"2025012305140954200_r11","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1084\/jem.20062602","article-title":"MyD88-dependent expansion of an immature GR-1(+) CD11b(+) population induces T cell suppression and Th2 polarization in sepsis","volume":"204","author":"Delano","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025012305140954200_r12","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1172\/JCI128075","article-title":"Post-sepsis immunosuppression depends on NKT cell regulation of mTOR\/IFN-\u03b3 in NK cells","volume":"130","author":"Kim","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2025012305140954200_r13","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.4049\/jimmunol.1202379","article-title":"Sustained and incomplete recovery of naive CD8+ T cell precursors after sepsis contributes to impaired CD8+ T cell responses to infection","volume":"190","author":"Condotta","year":"2013","journal-title":"J. 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Rheumatol."},{"key":"2025012305140954200_r45","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1038\/s41423-021-00750-4","article-title":"Activation or exhaustion of CD8+ T cells in patients with COVID-19","volume":"18","author":"Rha","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"2025012305140954200_r46","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1097\/00003246-199907000-00002","article-title":"Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction","volume":"27","author":"Hotchkiss","year":"1999","journal-title":"Crit. Care Med."},{"key":"2025012305140954200_r47","doi-asserted-by":"crossref","first-page":"7968","DOI":"10.4049\/jimmunol.177.11.7968","article-title":"The role of TCR engagement and activation-induced cell death in sepsis-induced T cell apoptosis","volume":"177","author":"Unsinger","year":"2006","journal-title":"J. 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