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.
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Tsukasa
T
Nabekura
Department of Immunology, Division of Biomedical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
Minoru
M
Kanaya
Department of Immunology, Division of Biomedical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
Akira
A
Shibuya
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Guo
G
Fu
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nicholas R J
NR
Gascoigne
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.
Lewis L
LL
Lanier
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002454:Cell Differentiation; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1