A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127

Christian A J Vosshenrich¹, Marcos E García-Ojeda¹, Sandrine I Samson-Villéger¹, Valerie Pasqualetto², Laurence Enault¹, Odile Richard-Le Goff¹, Erwan Corcuff¹, Delphine Guy-Grand¹, Benedita Rocha², Ana Cumano³, Lars Rogge⁴, Sophie Ezine² & James P Di Santo¹

¹  Unité des Cytokines et Développement Lymphoide, Institut National de la Santé et de la Recherche Médicale U668, Institut Pasteur, Paris F-75724, France.

²  Institut National de la Santé et de la Recherche Médicale U591, Faculté Necker Enfants Malades, Paris F-75015, France.

³  Unité de Développement des Lymphocytes, Institut National de la Santé et de la Recherche Médicale U668, Institut Pasteur, Paris F-75724, France

⁴  G5 Immunoregulation, Institut Pasteur, Paris F-75724, France.

Natural killer (NK) cell development is thought to occur in the bone marrow. Here we identify the transcription factor GATA-3 and CD127 (IL-7R) 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 (CD11b^loCD16^-CD69^hiLy49^lo) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56^hiCD16^- 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.

	Top