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Abstract

Natural killer (NK) cells play a critical role in host defense against tumors and intracellular pathogens. Eomesodermin (Eomes) and T-bet are T-box transcription factors that direct fate and function in cytotoxic lineages, such as CD8+ T cells and NK cells. Eomes and T-bet redundantly regulate differentiation of CD8+ effector T cells. Here we report that Eomes and T-bet play complementary and non-redundant roles in NK cell development. We find that conventional, CD49b-expressing (DX5+) NK cells fail to develop in the absence of Eomes. T-bet, however, is dispensable for the formation of conventional NK cells, even though this lineage expresses both T-bet and Eomes. Eomes-dependent, DX5+ NK cells are absent in neonatal mice. Instead, non-canonical, immature-appearing NK cells, characterized by the expression of the death ligand TRAIL, comprise the early neonatal NK cell repertoire. Non-canonical NK cells express T-bet but not Eomes and are absent in animals lacking T-bet. T-bet-dependent, TRAIL+ NK cells are less prevalent in lymphoid tissue of adult mice but represent a major subset of NK cells in the adult liver. In animals lacking both Eomes and T-bet, we find that neither Eomes-dependent, DX5+ NK cells nor T-bet-dependent, TRAIL+ NK cells develop, and that double mutant mice are devoid of all NK cells. Eomes and T-bet thus coordinate transcriptional programs required for development of two genetically, phenotypically, and functionally distinct NK cell lineages.

Copyright © 2011 by The American Association of Immunologists, Inc.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/pages/standard-publication-reuse-rights)
Issue Section:
Hematopoiesis
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