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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Cell Differentiation*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / physiopathology
  • Disease Models, Animal
  • Immunity, Innate / genetics
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Muromegalovirus / immunology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen