{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:20:28Z","timestamp":1791523228510,"version":"4.3.4"},"posted":{"date-parts":[[2026,3,1]]},"group-title":"Neuroscience","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Carol and Gene Ludwig Award for Neurodegeneration Research"},{"name":"National Institute of Health","award":["AG085374"],"award-info":[{"award-number":["AG085374"]}]},{"name":"National Institute of Health","award":["NS090934"],"award-info":[{"award-number":["NS090934"]}]},{"DOI":"10.13039\/100015595","name":"GHR Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015595","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05nzwyq50","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer\u2019s Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/003q4qk22","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AARF-23-1142708"],"award-info":[{"award-number":["AARF-23-1142708"]}],"id":[{"id":"https:\/\/ror.org\/0375f4d26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  There are changes in adaptive immunity in Alzheimer\u2019s disease (AD) and increases in activated CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells in brain correlate with tau pathology\n                  <jats:sup>1\u20133<\/jats:sup>\n                  . However, which cells mediate T cell priming in tau-mediated neurodegeneration remains unclear. In different conditions such as cancer, viral infections, and autoimmune diseases outside the CNS, conventional type-1 dendritic cells (cDC1) perform antigen cross-presentation to prime CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells\n                  <jats:sup>4,5<\/jats:sup>\n                  . We demonstrate that tauopathy mice deficient in cDC1 are markedly protected against tau-mediated neurodegeneration and display a selective decrease in brain CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell infiltration and glial reactivity. The remaining CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells showed an antigen inexperienced status with less clonal expansion, indicating suboptimal T cell priming. We confirm that brain derived antigens are presented in secondary lymphoid tissues to prime CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells. Our study identifies cDC1 cells as critical for CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell priming outside the CNS. This priming is required for a large increase of activated CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells in the brain which promotes tau-mediated neurodegeneration.\n                <\/jats:p>","DOI":"10.64898\/2026.02.26.708260","type":"posted-content","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T19:35:14Z","timestamp":1772393714000},"source":"Crossref","is-referenced-by-count":3,"title":["CD8\n                  <sup>+<\/sup>\n                  T cells are primed by cDC1 and exacerbate tau-mediated neurodegeneration"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-9897","authenticated-orcid":false,"given":"Hao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Bor-Chian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carisa","family":"Zeng","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabal","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Nulman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray A.","family":"Ohara","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne M.","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-4212","authenticated-orcid":false,"given":"Maxim N.","family":"Artyomov","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3505-9630","authenticated-orcid":false,"given":"Kenneth M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, 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