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J Exp Med. 2016 Nov 14;213(12):2745-2758. Epub 2016 Oct 24.

Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.
2
Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143.
3
Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan.
4
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 Lewis.Lanier@ucsf.edu.

Abstract

Natural killer (NK) cells provide important host defense and can generate long-lived memory NK cells. Here, by using novel transgenic mice carrying inducible Cre expressed under the control of Ncr1 gene, we demonstrated that two distinct long-lived NK cell subsets differentiate in a mouse model of cytomegalovirus (MCMV) infection. NK cells expressing the MCMV-specific Ly49H receptor differentiated into memory NK cells by an activating signaling through Ly49H and Ly49H- NK cells differentiated into cytokine-activated NK cells by exposure to inflammatory cytokines during infection. Interleukin-12 is indispensable for optimal generation of both antigen-specific memory NK cells and cytokine-activated NK cells. MCMV-specific memory NK cells show enhanced effector function and augmented antitumor activity in vivo as compared with cytokine-activated NK cells, whereas cytokine-activated NK cells exhibited a more robust response to IL-15 and persisted better in an MCMV-free environment. These findings reveal that NK cells are capable of differentiation into distinct long-lived subsets with different functional properties.

PMID:
27810928
PMCID:
PMC5110025
DOI:
10.1084/jem.20160726
[Indexed for MEDLINE]
Free PMC Article

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