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Immunity. 2014 Feb 20;40(2):225-34. doi: 10.1016/j.immuni.2013.12.011. Epub 2014 Jan 16.

Costimulatory molecule DNAM-1 is essential for optimal differentiation of memory natural killer cells during mouse cytomegalovirus infection.

Author information

1
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Department of Immunology, Division of Biomedical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
3
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: lewis.lanier@ucsf.edu.

Abstract

Recent studies demonstrate that natural killer (NK) cells have adaptive immune features. Here, we investigated the role of the costimulatory molecule DNAM-1 in the differentiation of NK cells in a mouse model of cytomegalovirus (MCMV) infection. Antibody blockade of DNAM-1 suppressed the expansion of MCMV-specific Ly49H(+) cells during viral infection and inhibited the generation of memory NK cells. Similarly, DNAM-1-deficient (Cd226(-/-)) Ly49H(+) NK cells exhibited intrinsic defects in expansion and differentiation into memory cells. Src-family tyrosine kinase Fyn and serine-threonine protein kinase C isoform eta (PKCη) signaling through DNAM-1 played distinct roles in the generation of MCMV-specific effector and memory NK cells. Thus, cooperative signaling through DNAM-1 and Ly49H are required for NK cell-mediated host defense against MCMV infection.

PMID:
24440149
PMCID:
PMC3943894
DOI:
10.1016/j.immuni.2013.12.011
[Indexed for MEDLINE]
Free PMC Article
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