'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection

• Published in: Nature immunology Vol. 11; no. 4; pp. 321 - 327
• Main Authors: Murphy, William J, Orr, Mark T, Lanier, Lewis L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-04-2010; Nature Publishing Group
• Subjects: 631/136/2091; 631/250/1619/382; 631/250/21/324/1509; 631/250/255/2514; Animals; Biomedical and Life Sciences; Biomedicine; Cytomegalovirus infections; Cytomegalovirus Infections - immunology; Cytotoxicity, Immunologic - immunology; Development and progression; Genetic aspects; Health aspects; Histocompatibility Antigens Class I - immunology; Immunology; Infectious Diseases; Killer cells; Killer Cells, Natural - immunology; Licensing; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Murine cytomegalovirus; NK Cell Lectin-Like Receptor Subfamily A - immunology; Phosphatases; Physiological aspects; Protein Tyrosine Phosphatase, Non-Receptor Type 6 - immunology; Rodent control; United States
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.1849

The importance of natural killer cell 'licensing'
in vivo
remains unclear. Lanier and co-workers now report that 'unlicensed' natural killer cells are more protective than 'licensed' cells during viral infection.
Natural killer (NK) cells expressing inhibitory receptors that bind to self major histocompatibility complex (MHC) class I are 'licensed', or rendered functionally more responsive to stimulation, whereas 'unlicensed' NK cells lacking receptors for self MHC class I are hyporesponsive. Here we show that contrary to the licensing hypothesis, unlicensed NK cells were the main mediators of NK cell–mediated control of mouse cytomegalovirus infection
in vivo.
Depletion of unlicensed NK cells impaired control of viral titers, but depletion of licensed NK cells did not. The transfer of unlicensed NK cells was more protective than was the transfer of licensed NK cells. Signaling by the tyrosine phosphatase SHP-1 limited the proliferation of licensed NK cells but not that of unlicensed NK cells during infection. Thus, unlicensed NK cells are critical for protection against viral infection.