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Article: Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity

TitleNatural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8<sup>+</sup> T-cell immunity
Authors
KeywordsNK cell activation
Virus persistence
Effector T cells
Virus elimination
Regulatory innate immunity
Issue Date2012
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 4, p. 1210-1215 How to Cite?
AbstractInfections 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.
Persistent Identifierhttp://hdl.handle.net/10722/292710
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLang, Philipp A.-
dc.contributor.authorLang, Karl S.-
dc.contributor.authorXu, Haifeng C.-
dc.contributor.authorGrusdat, Melanie-
dc.contributor.authorParish, Ian A.-
dc.contributor.authorRecher, Mike-
dc.contributor.authorElford, Alisha R.-
dc.contributor.authorDhanji, Salim-
dc.contributor.authorShaabani, Namir-
dc.contributor.authorTran, Charles W.-
dc.contributor.authorDissanayake, Dilan-
dc.contributor.authorRahbar, Ramtin-
dc.contributor.authorGhazarian, Magar-
dc.contributor.authorBrüstle, Anne-
dc.contributor.authorFine, Jason-
dc.contributor.authorChen, Peter-
dc.contributor.authorWeaver, Casey T.-
dc.contributor.authorKlose, Christoph-
dc.contributor.authorDiefenbach, Andreas-
dc.contributor.authorHäussinger, Dieter-
dc.contributor.authorCarlyle, James R.-
dc.contributor.authorKaech, Susan M.-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorOhashi, Pamela S.-
dc.date.accessioned2020-11-17T14:57:03Z-
dc.date.available2020-11-17T14:57:03Z-
dc.date.issued2012-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 4, p. 1210-1215-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292710-
dc.description.abstractInfections 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.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectNK cell activation-
dc.subjectVirus persistence-
dc.subjectEffector T cells-
dc.subjectVirus elimination-
dc.subjectRegulatory innate immunity-
dc.titleNatural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8<sup>+</sup> T-cell immunity-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1118834109-
dc.identifier.pmid22167808-
dc.identifier.pmcidPMC3268324-
dc.identifier.scopuseid_2-s2.0-84863011076-
dc.identifier.volume109-
dc.identifier.issue4-
dc.identifier.spage1210-
dc.identifier.epage1215-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000299412600046-
dc.identifier.f1000717952761-
dc.identifier.issnl0027-8424-

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