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dc.contributor.authorBahl, Kapil
dc.contributor.authorHubner, Anette
dc.contributor.authorDavis, Roger J.
dc.contributor.authorWelsh, Raymond M.
dc.date2022-08-11T08:08:17.000
dc.date.accessioned2022-08-23T15:49:08Z
dc.date.available2022-08-23T15:49:08Z
dc.date.issued2010-05-01
dc.date.submitted2016-05-25
dc.identifier.citationJ Virol. 2010 May;84(10):4866-77. doi: 10.1128/JVI.02571-09. Epub 2010 Mar 3. <a href="http://dx.doi.org/10.1128/JVI.02571-09">Link to article on publisher's site</a>
dc.identifier.issn0022-538X (Linking)
dc.identifier.doi10.1128/JVI.02571-09
dc.identifier.pmid20200235
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28360
dc.description.abstractProfound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the rapid clearance of apoptotic cells in vivo. Instead, a high frequency of annexin V-reactive CD8alpha(+) dendritic cells (DCs), which are known to be highly phagocytic, accumulated in the spleen as the memory T cell populations disappeared. After short in vitro incubation, memory phenotype T cells isolated from LCMV-infected mice (day 3) or mice treated with poly(I:C) (12 h) displayed substantial DNA fragmentation, as detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, compared to T cells isolated from uninfected mice, indicating a role for apoptosis in the memory T cell attrition. This apoptosis of memory CD8 T cells early during LCMV infection was reduced in mice lacking the proapoptotic molecule Bim. Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20200235&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsPublisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectMolecular Biology
dc.subjectVirology
dc.titleAnalysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists
dc.typeJournal Article
dc.source.journaltitleJournal of virology
dc.source.volume84
dc.source.issue10
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1084&amp;context=davis&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/davis/85
dc.identifier.contextkey8646731
refterms.dateFOA2022-08-23T15:49:08Z
html.description.abstract<p>Profound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the rapid clearance of apoptotic cells in vivo. Instead, a high frequency of annexin V-reactive CD8alpha(+) dendritic cells (DCs), which are known to be highly phagocytic, accumulated in the spleen as the memory T cell populations disappeared. After short in vitro incubation, memory phenotype T cells isolated from LCMV-infected mice (day 3) or mice treated with poly(I:C) (12 h) displayed substantial DNA fragmentation, as detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, compared to T cells isolated from uninfected mice, indicating a role for apoptosis in the memory T cell attrition. This apoptosis of memory CD8 T cells early during LCMV infection was reduced in mice lacking the proapoptotic molecule Bim. Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells.</p>
dc.identifier.submissionpathdavis/85
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages4866-77


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