Maturation of mouse NK cells is a 4-stage developmental program.
Surface density of CD27 and CD11b subdivides mouse natural killer (NK) cells into 4 subsets: CD11b(low)CD27(low), CD11b(low)CD27(high), CD11b(high)CD27(high), and CD11b(high)CD27(low). 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 CD11b(low)CD27(low) --> CD11b(low)CD27(high) --> CD11b(high)CD27(high) --> CD11b(high)CD27(low). This developmental program appears to be associated with a progressive acquisition of NK-cell effector functions.
Chiossone
Laura
L
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France.
Chaix
Julie
J
Fuseri
Nicolas
N
Roth
Claude
C
Vivier
Eric
E
Walzer
Thierry
T
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000276:immunology / Q000494:pharmacology; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
D039481:CD11b Antigen; D004167:Diphtheria Toxin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins