'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection
Open Access
- 28 February 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 11 (4), 321-327
- https://doi.org/10.1038/ni.1849
Abstract
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.Keywords
This publication has 50 references indexed in Scilit:
- Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infectionThe Journal of Experimental Medicine, 2009
- Ly49P recognition of cytomegalovirus-infected cells expressing H2-Dk and CMV-encoded m04 correlates with the NK cell antiviral responseThe Journal of Experimental Medicine, 2009
- Adaptive immune features of natural killer cellsNature, 2009
- Inhibitory Receptor Signaling via Tyrosine Phosphorylation of the Adaptor CrkImmunity, 2008
- Tolerance of NK cells encountering their viral ligand during developmentThe Journal of Experimental Medicine, 2008
- Continuous engagement of a self-specific activation receptor induces NK cell toleranceThe Journal of Experimental Medicine, 2008
- Up on the tightrope: natural killer cell activation and inhibitionNature Immunology, 2008
- HLA alleles determine differences in human natural killer cell responsiveness and potencyProceedings of the National Academy of Sciences of the United States of America, 2008
- Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantationClinical and Experimental Immunology, 2007
- Epistasis between mouse Klra and major histocompatibility complex class I loci is associated with a new mechanism of natural killer cell–mediated innate resistance to cytomegalovirus infectionNature Genetics, 2005