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

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 alpha) 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(Io)CD16(-)CD69(hi)Ly49(Io)) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56(hi)CD16(-) 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.