{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:56:39Z","timestamp":1790819799574,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,27]]},"group-title":"Immunology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01-AG078761"],"award-info":[{"award-number":["R01-AG078761"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01-CA269455-01A1"],"award-info":[{"award-number":["R01-CA269455-01A1"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  T cells persist in the central nervous system (CNS) and can drive both protection and neurological disease. How these cells are organized in humans and what they recognize is largely unknown. Here, we profiled CD8\u25a1 T cells across anatomically distinct CNS regions, obtained through on-site autopsies and temporal lobe resection surgeries, using single-cell RNA sequencing, paired T cell receptor sequencing, and DNA-barcoded tetramers. Resident memory T cells (T\n                  <jats:sub>RM<\/jats:sub>\n                  ) specific for Epstein-Barr virus, cytomegalovirus, influenza A, and SARS-CoV-2 were identified across CNS compartments. Anatomical location was the strongest correlate of T\n                  <jats:sub>RM<\/jats:sub>\n                  cell state, with leptomeningeal cells adopting a cytokine-poised T\n                  <jats:sub>RM<\/jats:sub>\n                  program, whereas brain T\n                  <jats:sub>RM<\/jats:sub>\n                  cells were transcriptionally restrained. Cells of the same clonotype spanned tissues yet adopted local transcriptional states. Viral specificity added another layer of T\n                  <jats:sub>RM<\/jats:sub>\n                  heterogeneity with\n                  <jats:italic>GZMK\/GZMA-<\/jats:italic>\n                  expressing EBV-specific populations and interferon-stimulated gene signatures in SARS-CoV-2 and Influenza A-specific cells. The human CNS thus harbors regionally distinct CD8\n                  <jats:sup>+<\/jats:sup>\n                  T\n                  <jats:sub>RM<\/jats:sub>\n                  shaped by common viral exposures.\n                <\/jats:p>","DOI":"10.64898\/2026.09.21.753190","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:30:10Z","timestamp":1790569810000},"source":"Crossref","is-referenced-by-count":0,"title":["Common viral infections seed regionally distinct resident memory T cells in the human CNS"],"prefix":"10.64898","author":[{"given":"Hanna N.","family":"Degefu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler G.","family":"Searles","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn C.","family":"Musial","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan F.","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra A.","family":"Kleist","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, Dartmouth College, Lebanon NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred W.","family":"Kolling","sequence":"additional","affiliation":[{"name":"Dartmouth Cancer Center, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jo","family":"Turk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"},{"name":"Dartmouth Cancer Center, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G J","family":"Skorput","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dartmouth Health, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Dartmouth Cancer Center, Lebanon, NH"},{"name":"Department of Pathology and Laboratory Medicine, Dartmouth Health, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Zanazzi","sequence":"additional","affiliation":[{"name":"Dartmouth Cancer Center, Lebanon, NH"},{"name":"Department of Pathology and Laboratory Medicine, Dartmouth Health, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dartmouth Health, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"},{"name":"Dartmouth Cancer Center, Lebanon, NH"},{"name":"Department of Biomedical Data Science, Dartmouth College, Lebanon NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela C.","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH"},{"name":"Dartmouth Cancer Center, Lebanon, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026093018050941000_2026.09.21.753190v1.1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/s41577-025-01175-0","article-title":"Redefining CNS immune privilege","volume":"25","year":"2025","journal-title":"Nat. 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