Brief Definit ive Report

NK cells are innate lymphocytes that kill virally infected and malignant cells. Their importance for the control of disease is highlighted by the susceptibility of NK-deficient patients to viral infections (Orange, 2006). NK cells also play a role preventing the development and progres-sion of cancer: cancer deaths are less frequent in patients who have higher levels of natural cyto-toxic activity (Imai et al., 2000), and stem cell transplant–derived NK cells are an important determinant of survival after radiotherapy for acute myeloid leukemia (Velardi et al., 2012). NK cells develop in bone marrow from com-mon lymphoid progenitors (CLPs; Kondo et al., 1997), which derive from lymphoid-primed multipotent progenitors (LMPPs; Adolfsson et al., 2005). NK progenitors (NKPs) were origi-nally defined as Lin NK1.1 DX5 CD122+ (Rosmaraki et al., 2001), but the progenitor fre-quency in this population is only 1 in 12, so the majority of these cells are not NKPs. Re-cently, the NKP phenotype has been refined, identifying populations that contain NKPs at a frequency of one in two (Carotta et al., 2011; Fathman et al., 2011). Several transcription factors that affect NK production have been identified, and the pheno-types of their knockouts suggest that these genes are required at different stages in development. Both immature and mature NK (iNK and mNK, respectively) numbers are reduced in the absence of Ets1 (Ramirez et al., 2012), T-bet (Townsen