'Unlicensed' natural killer cells dominate the response to cytomegalovirus 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.
Orr
Mark T
MT
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, California, USA.
Murphy
William J
WJ
Lanier
Lewis L
LL
D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse