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dc.contributor.authorWaggoner, Stephen N.
dc.contributor.authorTaniguchi, Ruth T.
dc.contributor.authorMathew, Porunelloor A.
dc.contributor.authorKumar, Vinay
dc.contributor.authorWelsh, Raymond M.
dc.date2022-08-11T08:09:40.000
dc.date.accessioned2022-08-23T16:39:13Z
dc.date.available2022-08-23T16:39:13Z
dc.date.issued2010-05-05
dc.date.submitted2010-07-01
dc.identifier.citationJ Clin Invest. 2010 Jun 1;120(6):1925-38. doi: 10.1172/JCI41264. Epub 2010 May 3. <a href="http://dx.doi.org/10.1172/JCI41264">Link to article on publisher's site</a>
dc.identifier.issn0021-9738 (Linking)
dc.identifier.doi10.1172/JCI41264
dc.identifier.pmid20440077
dc.identifier.pmid20440077
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39426
dc.description.abstractPersistent viral infections are often associated with inefficient T cell responses and sustained high-level expression of inhibitory receptors, such as the NK cell receptor 2B4 (also known as CD244), on virus-specific T cells. However, the role of 2B4 in T cell dysfunction is undefined, and it is unknown whether NK cells contribute to regulation of these processes. We show here that persistent lymphocytic choriomeningitis virus (LCMV) infection of mice lacking 2B4 resulted in diminished LCMV-specific CD8+ T cell responses, prolonged viral persistence, and spleen and thymic pathologies that differed from those observed in infected wild-type mice. Surprisingly, these altered phenotypes were not caused by 2B4 deficiency in T cells. Rather, the entire and long-lasting pathology and viral persistence were regulated by 2B4-deficient NK cells acting early in infection. In the absence of 2B4, NK cells lysed activated (defined as CD44hi) but not naive (defined as CD44lo) CD8+ T cells in a perforin-dependent manner in vitro and in vivo. These results illustrate the importance of NK cell self-tolerance to activated CD8+ T cells and demonstrate how an apparent T cell-associated persistent infection can actually be regulated by NK cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20440077&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectAntigens, CD3
dc.subjectKiller Cells, Natural
dc.subjectLymphocytic Choriomeningitis
dc.subjectLymphocytic choriomeningitis virus
dc.subjectMice
dc.subjectMice, Congenic
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectNK Cell Lectin-Like Receptor Subfamily D
dc.subjectPerforin
dc.subjectSpleen
dc.subjectT-Lymphocytes
dc.subjectImmunopathology
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectPathology
dc.titleAbsence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis
dc.typeJournal Article
dc.source.journaltitleThe Journal of clinical investigation
dc.source.volume120
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3219&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2220
dc.identifier.contextkey1378351
refterms.dateFOA2022-08-23T16:39:14Z
html.description.abstract<p>Persistent viral infections are often associated with inefficient T cell responses and sustained high-level expression of inhibitory receptors, such as the NK cell receptor 2B4 (also known as CD244), on virus-specific T cells. However, the role of 2B4 in T cell dysfunction is undefined, and it is unknown whether NK cells contribute to regulation of these processes. We show here that persistent lymphocytic choriomeningitis virus (LCMV) infection of mice lacking 2B4 resulted in diminished LCMV-specific CD8+ T cell responses, prolonged viral persistence, and spleen and thymic pathologies that differed from those observed in infected wild-type mice. Surprisingly, these altered phenotypes were not caused by 2B4 deficiency in T cells. Rather, the entire and long-lasting pathology and viral persistence were regulated by 2B4-deficient NK cells acting early in infection. In the absence of 2B4, NK cells lysed activated (defined as CD44hi) but not naive (defined as CD44lo) CD8+ T cells in a perforin-dependent manner in vitro and in vivo. These results illustrate the importance of NK cell self-tolerance to activated CD8+ T cells and demonstrate how an apparent T cell-associated persistent infection can actually be regulated by NK cells.</p>
dc.identifier.submissionpathoapubs/2220
dc.contributor.departmentDepartment of Pathology
dc.source.pages1925-38


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