{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:20:55Z","timestamp":1761312055659,"version":"3.41.2"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Antigen-driven human effector-memory CD8+ T cells expressing low levels of the CD8\u03b2 chain have been previously described. However, little is known on a possible antigen-independent trigger. We have examined the impact that IL-15 has on the expression of CD8\u03b2 on purified human na\u00efve CD8+ T cells after CFSE labeling and culture with IL-15. As expected, IL-15 induced na\u00efve CD8+ T cells to proliferate and differentiate. Remarkably, the process was associated with a cell-cycle dependent down-modulation of CD8\u03b2 from the cell surface, leading to the generation of CD8\u03b1\u03b2<jats:sup>low<\/jats:sup> and CD8\u03b1\u03b2<jats:sup>\u2212<\/jats:sup> (i.e., CD8\u03b1\u03b1) T cells. In contrast, expression of the CD8\u03b1 chain remained steady or even increased. Neither IL-2 nor IL-7 reproduced the effect of IL-15. Determination of mRNA levels for CD8\u03b1 and CD8\u03b2 isoforms by qPCR revealed that IL-15 promoted a significant decrease in mRNA levels of the CD8\u03b2 M-4 isoform, while levels of the M-1\/M-2 isoforms and of CD8\u03b1 increased. Noteworthy, CD8+ T cell blasts obtained after culture of CD8+ T cells with IL-15 showed a cell-cycle dependent increase in the level of the tyrosine kinase Lck, when compared to CD8+ T cells at day 0. This study has shown for the first time that IL-15 generates CD8\u03b1\u03b1<jats:sup>+<\/jats:sup>\u03b1\u03b2<jats:sup>low<\/jats:sup> and CD8\u03b1\u03b1<jats:sup>+<\/jats:sup>\u03b1\u03b2<jats:sup>\u2212<\/jats:sup> T cells containing high levels of Lck, suggesting that they may be endowed with unique functional features.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1252439","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T04:58:00Z","timestamp":1717563480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["In vitro IL-15-activated human na\u00efve CD8+ T cells down-modulate the CD8\u03b2 chain and become CD8\u03b1\u03b1 T cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Andr\u00e9 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