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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5488-5496.
Prepublished online as a Blood First Edition Paper on February 20, 2009; DOI 10.1182/blood-2008-10-187179.


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IMMUNOBIOLOGY

Maturation of mouse NK cells is a 4-stage developmental program

Laura Chiossone13, Julie Chaix13, Nicolas Fuseri4, Claude Roth5, Eric Vivier13,6, and Thierry Walzer13

1 Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille; 2 Inserm, U631, Marseille; 3 Centre National de la Recherche Scientifique (CNRS), UMR6102, Marseille; 4 Innate-Pharma, Marseille; 5 Département d'Immunologie, Institut Pasteur, Paris; and 6 Assistance Publique-Hôpitaux (AP-HP) de Marseille, Hôpital de la Conception, Marseille, France

Surface density of CD27 and CD11b subdivides mouse natural killer (NK) cells into 4 subsets: CD11blowCD27low, CD11blowCD27high, CD11bhighCD27high, and CD11bhighCD27low. To determine the developmental relationship between these 4 subsets, we used several complementary approaches. First, we took advantage of NDE transgenic mice that express enhanced green fluorescent protein (EGFP) and diphtheria toxin receptor specifically in NK cells. Diphtheria toxin injection leads to a transient depletion of NK cells, allowing the monitoring of the phenotype of developing EGFP+ NK cells after diphtheria toxin injection. Second, we evaluated the overall proximity between NK-cell subsets based on their global gene profile. Third, we compared the proliferative capacity of NK-cell subsets at steady state or during replenishment of the NK-cell pool. Fourth, we performed adoptive transfers of EGFP+ NK cell subsets from NDE mice into unirradiated mice and followed the fate of transferred cells. The results of these various experiments collectively support a 4-stage model of NK-cell maturation CD11blowCD27low -> CD11blowCD27high -> CD11bhighCD27high -> CD11bhighCD27low. This developmental program appears to be associated with a progressive acquisition of NK-cell effector functions.


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