Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection
Copyright policy )Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection
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.
- National University of Singapore Singapore
- University of California System United States
- Scripps Research Institute United States
- University of California, San Francisco United States
- University of Tsukuba Japan
Antigens, Differentiation, T-Lymphocyte, Muromegalovirus, Immunology, 610, Inbred C57BL, Mice, Biodefense, 2.1 Biological and endogenous factors, Innate, Killer Cells, Immunology and Allergy, Animals, Antigens, Biomedical and Clinical Sciences, T Lineage-Specific Activation Antigen 1, Animal, Inflammatory and immune system, Immunity, Cell Differentiation, Immunity, Innate, Killer Cells, Natural, Mice, Inbred C57BL, Disease Models, Animal, Emerging Infectious Diseases, Infectious Diseases, T-Lymphocyte, Differentiation, Disease Models, Cytomegalovirus Infections, Natural
Antigens, Differentiation, T-Lymphocyte, Muromegalovirus, Immunology, 610, Inbred C57BL, Mice, Biodefense, 2.1 Biological and endogenous factors, Innate, Killer Cells, Immunology and Allergy, Animals, Antigens, Biomedical and Clinical Sciences, T Lineage-Specific Activation Antigen 1, Animal, Inflammatory and immune system, Immunity, Cell Differentiation, Immunity, Innate, Killer Cells, Natural, Mice, Inbred C57BL, Disease Models, Animal, Emerging Infectious Diseases, Infectious Diseases, T-Lymphocyte, Differentiation, Disease Models, Cytomegalovirus Infections, Natural
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