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(lo) CD16- CD69(hi) Ly49(lo)) 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.
Vosshenrich
Christian A J
CA
Unité des Cytokines et Développement Lymphoide, Institut National de la Santé et de la Recherche Médicale U668, Institut Pasteur, Paris F-75724, France.
García-Ojeda
Marcos E
ME
Samson-Villéger
Sandrine I
SI
Pasqualetto
Valerie
V
Enault
Laurence
L
Richard-Le Goff
Odile
O
Corcuff
Erwan
E
Guy-Grand
Delphine
D
Rocha
Benedita
B
Cumano
Ana
A
Rogge
Lars
L
Ezine
Sophie
S
Di Santo
James P
JP
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D050990:GATA3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000502:physiology; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit