Abstract
Natural killer (NK) cell development is thought to occur in the bone marrow. Here we identify the transcription factor GATA-3 and CD127 (IL-7Rα) as molecular markers of a pathway of mouse NK cell development that originates in the thymus. Thymus-derived CD127+ NK cells repopulated peripheral lymphoid organs, and their homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK cells had a distinct phenotype (CD11bloCD16−CD69hiLy49lo) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56hiCD16− NK cells, which we found expressed CD127 and had more GATA-3 expression than human CD56+CD16+ NK cells. We propose that bone marrow and thymic NK cell pathways generate distinct mouse NK cells with properties similar to those of the two human CD56 NK cell subsets.
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Change history
03 November 2006
In the version of this article initially published, the symbols in the key of Figure 7a are incorrect. The filled ovals are Splenic; the filled diamonds are Thymic. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank B. Canque, G. de Saint Basile, E. Six and M. Albert for thymocytes, peripheral blood mononuclear cells and antibodies for human studies, and R. Hendriks for Gata3+/nlslacZ mice. Supported by the Institut Pasteur, the Institut National de la Santé et Recherche Medicale, the Ligue Nationale Contre le Cancer and the Fondation de la Recherche Médicale, as well as the Pasteur Foundation and Institut National de la Santé et Recherche Medicale (M.G.O.).
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C.A.J.V., M.E.G.-O., S.I.S.-V., L.E., D.G.-G., L.R., S.E. and J.P.D. did the experiments; V.P., O.R.-L. and E.C. provided technical assistance; B.R., A.C. and S.E. contributed to the experimental design and analysis; and C.A.J.V. and J.P.D. wrote the manuscript.
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Vosshenrich, C., García-Ojeda, M., Samson-Villéger, S. et al. A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol 7, 1217–1224 (2006). https://doi.org/10.1038/ni1395
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DOI: https://doi.org/10.1038/ni1395
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