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dc.contributor.authorIwakoshi, Neal N.
dc.contributor.authorGoldschneider, Irving
dc.contributor.authorTausche, Frances
dc.contributor.authorMordes, John P.
dc.contributor.authorRossini, Aldo A.
dc.contributor.authorGreiner, Dale L.
dc.date2022-08-11T08:08:59.000
dc.date.accessioned2022-08-23T16:14:38Z
dc.date.available2022-08-23T16:14:38Z
dc.date.issued1998-06-24
dc.date.submitted2008-10-09
dc.identifier.citation<p>J Immunol. 1998 Jun 15;160(12):5838-50.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.pmid9637495
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33907
dc.description.abstractDiabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic and circulate severely reduced numbers of T cells. Peripheral T cells present are phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-BB recent thymic emigrants have a shortened life span and disappear by apoptosis. The percentage of T cells with an alphabetaTCR(low) B220+ CD4- CD8- phenotype was increased in DP peripheral lymphoid tissues when compared with normal, nonlymphopenic diabetes-resistant (DR) BB rat tissues. There was no evidence of DNA fragmentation in freshly isolated DP- or DR-BB rat cells, but, after 24 h of culture, a higher proportion of DP- than DR-BB splenic T cells underwent apoptosis. We then tested the hypothesis that BB rat T cells with the alphabetaTCR(low) B220+ CD4- CD8- phenotype accumulate and undergo apoptosis in the liver. Such cells were observed undergoing apoptosis in both DP- and DR-BB rats, but comprised approximately 80% of intrahepatic T cells in DP vs approximately 20% in DR-BB rats. Most alphabetaTCR(low) B220+ CD4- CD8- cells in the liver were also Thy1+. The data suggest that T cell apoptosis in the DP-BB rat is underway in peripheral lymphoid tissues and is completed in the liver. Increased intrahepatic apoptosis of recent thymic emigrants appears in part responsible for lymphopenia in DP-BB rats and the concomitant predisposition of these animals to autoimmunity.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9637495&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttp://www.jimmunol.org/content/160/12/5838.long
dc.subjectAnimals; *Apoptosis; Diabetes Mellitus, Type 1; Female; Liver; Lymphopenia; Male; Rats; Rats, Inbred BB; Receptors, Antigen, T-Cell; T-Lymphocytes
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleHigh frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume160
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/562
dc.identifier.contextkey646747
html.description.abstract<p>Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic and circulate severely reduced numbers of T cells. Peripheral T cells present are phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-BB recent thymic emigrants have a shortened life span and disappear by apoptosis. The percentage of T cells with an alphabetaTCR(low) B220+ CD4- CD8- phenotype was increased in DP peripheral lymphoid tissues when compared with normal, nonlymphopenic diabetes-resistant (DR) BB rat tissues. There was no evidence of DNA fragmentation in freshly isolated DP- or DR-BB rat cells, but, after 24 h of culture, a higher proportion of DP- than DR-BB splenic T cells underwent apoptosis. We then tested the hypothesis that BB rat T cells with the alphabetaTCR(low) B220+ CD4- CD8- phenotype accumulate and undergo apoptosis in the liver. Such cells were observed undergoing apoptosis in both DP- and DR-BB rats, but comprised approximately 80% of intrahepatic T cells in DP vs approximately 20% in DR-BB rats. Most alphabetaTCR(low) B220+ CD4- CD8- cells in the liver were also Thy1+. The data suggest that T cell apoptosis in the DP-BB rat is underway in peripheral lymphoid tissues and is completed in the liver. Increased intrahepatic apoptosis of recent thymic emigrants appears in part responsible for lymphopenia in DP-BB rats and the concomitant predisposition of these animals to autoimmunity.</p>
dc.identifier.submissionpathgsbs_sp/562
dc.contributor.departmentDepartment of Medicine, Diabetes Division
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentProgram in Immunology and Virology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages5838-50


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