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

Mark T. Orr, William J Murphy, Lewis L. Lanier

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalNature Immunology
Volume11
Issue number4
DOIs
StatePublished - 2010

Fingerprint

Cytomegalovirus Infections
Natural Killer Cells
Natural Killer Cell Receptors
Major Histocompatibility Complex
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Muromegalovirus
Cytoprotection
Virus Diseases
Licensure
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection. / Orr, Mark T.; Murphy, William J; Lanier, Lewis L.

In: Nature Immunology, Vol. 11, No. 4, 2010, p. 321-327.

Research output: Contribution to journalArticle

@article{8cf0965d31e647e08dbb8af6b5bd249c,
title = "'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection",
abstract = "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.",
author = "Orr, {Mark T.} and Murphy, {William J} and Lanier, {Lewis L.}",
year = "2010",
doi = "10.1038/ni.1849",
language = "English (US)",
volume = "11",
pages = "321--327",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - 'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection

AU - Orr, Mark T.

AU - Murphy, William J

AU - Lanier, Lewis L.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77949824940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949824940&partnerID=8YFLogxK

U2 - 10.1038/ni.1849

DO - 10.1038/ni.1849

M3 - Article

C2 - 20190757

AN - SCOPUS:77949824940

VL - 11

SP - 321

EP - 327

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 4

ER -