Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity
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Lang, Philipp A; Lang, Karl S.; Xu, Haifeng C/; Grusdat, Melanie; Parish, Ian; Recher, Mike; Elford, Alisha R.; Dhanji, Salim; Shaabani, Namir; Tran, Charles W.; Dissanayake, Dilan; Rahbar, Ramtin; Ghazarian, Magar; Brustle, Anne
Description
Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease.Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus.NK cell-deficient (Nfil3 -/-, E4BP4 -/-)mice exhibited...[Show more]
dc.contributor.author | Lang, Philipp A | |
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dc.contributor.author | Lang, Karl S. | |
dc.contributor.author | Xu, Haifeng C/ | |
dc.contributor.author | Grusdat, Melanie | |
dc.contributor.author | Parish, Ian | |
dc.contributor.author | Recher, Mike | |
dc.contributor.author | Elford, Alisha R. | |
dc.contributor.author | Dhanji, Salim | |
dc.contributor.author | Shaabani, Namir | |
dc.contributor.author | Tran, Charles W. | |
dc.contributor.author | Dissanayake, Dilan | |
dc.contributor.author | Rahbar, Ramtin | |
dc.contributor.author | Ghazarian, Magar | |
dc.contributor.author | Brustle, Anne | |
dc.date.accessioned | 2015-12-10T22:55:00Z | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.uri | http://hdl.handle.net/1885/59901 | |
dc.description.abstract | Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease.Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus.NK cell-deficient (Nfil3 -/-, E4BP4 -/-)mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILEinfected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore,we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection. | |
dc.publisher | National Academy of Sciences (USA) | |
dc.rights | Author/s retain copyright | |
dc.source | PNAS - Proceedings of the National Academy of Sciences of the United States of America | |
dc.subject | Keywords: perforin; animal cell; animal experiment; article; CD8+ T lymphocyte; cell activation; cell function; cellular immunity; controlled study; immunopathology; in vivo study; infection prevention; mouse; natural killer cell; nonhuman; priority journal; virus Effector T cells; NK cell activation; Regulatory innate immunity; Virus elimination; Virus persistence | |
dc.title | Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 109 | |
dc.date.issued | 2012 | |
local.identifier.absfor | 110799 - Immunology not elsewhere classified | |
local.identifier.ariespublication | U3488905xPUB513 | |
local.type.status | Published Version | |
local.contributor.affiliation | Lang, Philipp A, Ontario Cancer Institute | |
local.contributor.affiliation | Lang, Karl S., University of Dusseldorf | |
local.contributor.affiliation | Xu, Haifeng C/, Ontario Cancer Institute | |
local.contributor.affiliation | Grusdat, Melanie, University of Dusseldorf | |
local.contributor.affiliation | Parish, Ian, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Recher, Mike, Harvard Medical School | |
local.contributor.affiliation | Elford, Alisha R., Ontario Cancer Institute | |
local.contributor.affiliation | Dhanji, Salim, Ontario Cancer Institute | |
local.contributor.affiliation | Shaabani, Namir, University of Dusseldorf | |
local.contributor.affiliation | Tran, Charles W., Ontario Cancer Institute | |
local.contributor.affiliation | Dissanayake, Dilan, Ontario Cancer Institute | |
local.contributor.affiliation | Rahbar, Ramtin, Ontario Cancer Institute | |
local.contributor.affiliation | Ghazarian, Magar, Ontario Cancer Institute | |
local.contributor.affiliation | Brustle, Anne, Ontario Cancer Institute | |
local.bibliographicCitation.issue | 4 | |
local.bibliographicCitation.startpage | 1210 | |
local.bibliographicCitation.lastpage | 1215 | |
local.identifier.doi | 10.1073/pnas.1118834109 | |
dc.date.updated | 2016-02-24T10:06:52Z | |
local.identifier.scopusID | 2-s2.0-84863011076 | |
dcterms.accessRights | Open Access | |
Collections | ANU Research Publications |
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