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Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection

  • Author(s): Nabekura, T
  • Kanaya, M
  • Shibuya, A
  • Fu, G
  • Gascoigne, NRJ
  • Lanier, LL
  • et al.
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. © 2014 Elsevier Inc.

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