Immunity
Volume 40, Issue 2, 20 February 2014, Pages 225-234
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Article
Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection

https://doi.org/10.1016/j.immuni.2013.12.011Get rights and content
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Highlights

  • DNAM-1 is required for the expansion and generation of memory NK cells

  • Fyn and PKCη play distinct role in DNAM-1 signaling in Ly49H+ NK cells

  • DNAM-1 is dynamically regulated on NK cells during MCMV infection

  • MCMV infection upregulates DNAM-1 ligands on dendritic cells and macrophages

Summary

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.

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Present address: Department of Microbiology, Yong Loo Lin School of Medicine, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore