{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:20:05Z","timestamp":1793733605318,"version":"4.6.1"},"reference-count":92,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"787","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,2,26]]},"abstract":"<jats:p>\n            Immune aplastic anemia (AA) is a life-threatening bone marrow failure disorder driven by an autoimmune T cell attack against hematopoietic stem and progenitor cells (HSPCs). However, the exact autoantigen targets and role of other immune cells in the pathogenesis of AA are unknown. Here, we analyzed a cohort of 218 patients with AA using single-cell RNA and T cell receptor (TCR) \u03b1\u03b2 sequencing, TCR\u03b2 sequencing, flow cytometry, and plasma cytokine profiling. We identified natural killer (NK) cells and CD8\n            <jats:sup>+<\/jats:sup>\n            terminally differentiated effector T (T\n            <jats:sub>EMRA<\/jats:sub>\n            ) cells expressing NK receptors with AA-associated TCR\u03b2 motifs as the most dysregulated immune cell populations in AA bone marrow. Functional coculture experiments using primary HSPCs and immune cells showed that NK cells cannot kill HSPCs alone but may sensitize HSPCs to CD8\n            <jats:sup>+<\/jats:sup>\n            T cell\u2013mediated killing through production of interferons. Furthermore, HSPCs induced activation of T cell clones with CD8\n            <jats:sup>+<\/jats:sup>\n            T\n            <jats:sub>EMRA<\/jats:sub>\n            NK-like phenotype in coculture. Our results reveal a convergent phenotype of innate and adaptive immune cells that may drive AA.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adl6758","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T18:59:56Z","timestamp":1740596396000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Single-cell analysis of aplastic anemia reveals a convergence of NK and NK-like CD8\n            <sup>+<\/sup>\n            T cells with a disease-associated TCR signature"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3146-9816","authenticated-orcid":true,"given":"Sofie","family":"Lundgren","sequence":"first","affiliation":[{"name":"Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki 00290, Finland."},{"name":"Translational Immunology Research 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