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We integrated single\u2010cell RNA sequencing (scRNA\u2010seq), paired single\u2010cell T cell receptor sequencing (scTCR\u2010seq), bulk RNA sequencing (RNA\u2010seq), and flow cytometry to characterize CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in septic shock\u2010associated immunosuppression. Patients showed reduced T cell receptor (TCR) clonotype diversity in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells but not CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, with restricted clonality correlating with disease severity and lymphopenia. Integrative analyses revealed the expansion of two disease\u2010associated subsets: (1) CD177\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, enriched for interleukin\u201017 (IL\u201017) signaling with hyperexpanded clonotypes, and (2) TLR4\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, enriched for phagocytosis\u2010 and lysosome\u2010related programs with restricted clonality. Both subsets expressed high levels of S100A8, S100A9, and S100A12, correlating positively with severity scores and systemic inflammation. These findings provided single\u2010cell resolution evidence that clonal restriction of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells is a hallmark of septic immunosuppression. Our study depicted a single\u2010cell atlas linking CD4\n                    <jats:sup>+<\/jats:sup>\n                    clonal restriction and the expansion of pathogenic T cell subsets to outcome, highlighting TCR clonality as a biomarker of immune competence and CD177\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    and TLR4\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells as candidate therapeutic targets in septic shock\u2010associated immunosuppression.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70927","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:07:11Z","timestamp":1786950431000},"source":"Crossref","is-referenced-by-count":0,"title":["Restricted TCR Diversity and Expansion of CD177\n                    <sup>+<\/sup>\n                    CD8\n                    <sup>+<\/sup>\n                    and TLR4\n                    <sup>+<\/sup>\n                    CD4\n                    <sup>+<\/sup>\n                    T Cell Subsets in Septic Shock\u2010Associated Immunosuppression: A Single\u2010Cell Multi\u2010Omics Study"],"prefix":"10.1002","volume":"7","author":[{"given":"Yawen","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunyao","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases Clinical and Science Investigation Institute Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College  Beijing 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