{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:01:30Z","timestamp":1772600490923,"version":"3.50.1"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Individual T cell responses vary significantly based on the microenvironment present at the time of immune response and on prior induced T cell memory. While the cecal ligation and puncture (CLP) model is the most commonly used murine sepsis model, the contribution of diverse T cell responses has not been explored. We defined T cell subset responses to CLP using single-cell RNA sequencing and examined the effects of prior induced T cell memory (Immune Education) on these responses. We hypothesized that Immune Education prior to CLP would alter T cell responses at the single cell level at a single, early post-CLP time point.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Splenic T cells were isolated from C57BL\/6 mice. Four cohorts were studied: Control, Immune-Educated, CLP, and Immune-Educated CLP. At age 8 weeks, Immune-Educated and Immune-Educated CLP mice received anti-CD3\u03f5 antibody; Control and CLP mice were administered an isotype control. CLP (two punctures with a 22-gauge needle) was performed at 12-13 weeks of life. Mice were sacrificed at baseline or 24-hours post-CLP. Unsupervised clustering of the transcriptome library identified six distinct T cell subsets: quiescent na\u00efve CD4<jats:sup>+<\/jats:sup>, primed na\u00efve CD4<jats:sup>+<\/jats:sup>, memory CD4<jats:sup>+<\/jats:sup>, na\u00efve CD8<jats:sup>+<\/jats:sup>, activated CD8<jats:sup>+<\/jats:sup>, and CD8<jats:sup>+<\/jats:sup> cytotoxic T cell subsets. T cell subset specific gene set enrichment analysis and Hurdle analysis for differentially expressed genes (DEGs) were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>T cell responses to CLP were not uniform \u2013 subsets of activated and suppressed T cells were identified. Immune Education augmented specific T cell subsets and led to genomic signatures favoring T cell survival in unoperated and CLP mice. Additionally, the combination of Immune Education and CLP effected the expression of genes related to T cell activity in ways that differed from CLP alone. Validating our finding that IL7R pathway markers were upregulated in Immune-Educated CLP mice, we found that Immune Education increased T cell surface IL7R expression in post-CLP mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Immune Education enhanced the expression of genes associated with T cell survival in unoperated and CLP mice. Induction of memory T cell compartments via Immune Education combined with CLP may increase the model\u2019s concordance to human sepsis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1366955","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:56:35Z","timestamp":1710737795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-cell RNA sequencing reveals Immune Education promotes T cell survival in mice subjected to the cecal ligation and puncture sepsis model"],"prefix":"10.3389","volume":"15","author":[{"given":"Steven D.","family":"Ham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabel N.","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford 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