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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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Submitted October 31, 2008
Accepted February 16, 2009
Maturation of mouse NK cells is a four-stage developmental program
Laura Chiossone, Julie Chaix, Nicolas Fuseri, Claude Roth, Eric Vivier, and Thierry Walzer*
Centre d'Immunologie de Marseille-Luminy, Universite de la Mediterranee, Marseille, France
INSERM, U631, Marseille, France
Innate-Pharma, Marseille, France
Departement d'Immunologie, Institut Pasteur, Paris, France
Assistance Publique - Hopitaux de Marseille, Hopital de la Conception, Marseille, France
CNRS, UMR6102, Marseille, France
* Corresponding author; email: walzer{at}ciml.univ-mrs.fr.
Surface density of CD27 and CD11b subdivides mouse NK cells into four subsets: CD11blowCD27low CD11blowCD27high, CD11bhighCD27high and CD11bhighCD27low. To determine the developmental relationship between these four subsets, we used several complementary approaches. First, we took advantage of NDE transgenic mice that express EGFP and diphtheria toxin receptor specifically in NK cells. DT injection leads to a transient depletion of NK cells, allowing to monitor the phenotype of developing EGFP+ NK cells after DT 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 positive 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 four-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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