THE ETS-1 TRANSCRIPTION FACTOR IS REQUIRED FOR THE DEVELOPMENT OF NATURAL-KILLER-CELLS IN MICE

In this report we have investigated the role of the Ets-1 transcriptio n factor in the differentiation of the NK cell lineage in mice. Spleni c NK cells express high levels of Ets-1. Ets-1-deficient mice produced by gene targeting developed mature erythrocytes, monocytes, neutrophi ls, and T and B lymphocytes. However, spleens from the Ets-1-deficient mice contained significantly reduced numbers of natural killer (NK) c ells, and splenocytes from these mice lacked detectable cytolytic acti vity against NK cell targets in vitro. Moreover, unlike wild-type anim als, Ets-1-deficient mice developed tumors following subcutaneous inje ction of NK susceptible RMA-S cells. These NK cell defects could not b e correlated with defects in the expression of IL-12, IL-15, and IL-18 or the IL-2 or IL-15 receptors. Thus, Ets-1 defines a novel transcrip tional pathway that is required for the development of the NK cell lin eage in mice.