Abstract
In this report we have investigated the role of the Ets-1 transcription factor in the differentiation of the NK cell lineage in mice. Splenic NK cells express high levels of Ets-1. Ets-1-deficient mice produced by gene targeting developed mature erythrocytes, monocytes, neutrophils, and T and B lymphocytes. However, spleens from the Ets-1-deficient mice contained significantly reduced numbers of natural killer (NK) cells, and splenocytes from these mice lacked detectable cytolytic activity against NK cell targets in vitro. Moreover, unlike wild-type animals, Ets-1-deficient mice developed tumors following subcutaneous injection of NK-susceptible RMA-S cells. These NK cell defects could not be 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 transcriptional pathway that is required for the development of the NK cell lineage in mice.
Original language | English (US) |
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Pages (from-to) | 555-563 |
Number of pages | 9 |
Journal | Immunity |
Volume | 9 |
Issue number | 4 |
DOIs | |
State | Published - Oct 1998 |
Funding
We thank T. Ley for the generous gift of the RW ES cells, P. Cresswell for the RMA-S cells, and C. Clendenin and K. Sigrist for help with the generation of the Ets-1-deficient mice. L. Gottschalk helped with the preparation of illustrations. P. Lawrey assisted with the preparation of the manuscript. This work was supported in part by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (to J. L.) and by the Cancer Center of the University of Chicago. DNAX is supported by Schering-Plough Corporation.
ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
- Immunology