{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:26:27Z","timestamp":1790814387351,"version":"4.1.0"},"reference-count":81,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":65,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F30AI161318,R01CA205239,P50CA171963,P30CA91842,T32GM139799,F31GM146361,T32HL007088"],"award-info":[{"award-number":["F30AI161318,R01CA205239,P50CA171963,P30CA91842,T32GM139799,F31GM146361,T32HL007088"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI13030"],"award-info":[{"award-number":["R01AI13030"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5K12CA167540"],"award-info":[{"award-number":["5K12CA167540"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:p>\n                    The surface receptor CD8\u03b1 is present on 20%\u201380% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8\u03b1 expression on donor NK cells was associated with a lack of therapeutic responses in patients with leukemia in prior studies, thus, we hypothesized that CD8\u03b1 may affect critical NK cell functions. Here, we discovered that CD8\u03b1\n                    <jats:sup>\u2013<\/jats:sup>\n                    NK cells had improved control of leukemia in xenograft models compared with CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, we found that CD8\u03b1 expression was induced on approximately 30% of previously CD8\u03b1\n                    <jats:sup>\u2013<\/jats:sup>\n                    NK cells following IL-15 stimulation. These induced CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    (iCD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    ) NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity compared with those that sustained existing CD8\u03b1 expression (sustained CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    ) or those that remained CD8\u03b1\n                    <jats:sup>\u2013<\/jats:sup>\n                    (persistent CD8\u03b1\n                    <jats:sup>\u2013<\/jats:sup>\n                    ). These iCD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    cells originated from an IL-15R\u03b2\n                    <jats:sup>hi<\/jats:sup>\n                    NK cell population, with CD8\u03b1 expression dependent on the transcription factor RUNX3. Moreover,\n                    <jats:italic>CD8A<\/jats:italic>\n                    CRISPR\/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8\u03b1 status identified human NK cell capacity for IL-15\u2013induced proliferation and metabolism in a time-dependent fashion, and its presence had a suppressive effect on NK cell\u2013activating receptors.\n                  <\/jats:p>","DOI":"10.1172\/jci173602","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T14:05:16Z","timestamp":1722434716000},"source":"Crossref","is-referenced-by-count":21,"title":["Induced CD8\u03b1 identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0037-9324","authenticated-orcid":true,"given":"Celia C.","family":"Cubitt","sequence":"first","affiliation":[{"name":"Division of Oncology, Siteman Cancer Center, 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