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dc.contributor.authorWhalen, Barbara J.
dc.contributor.authorMarounek, Jan
dc.contributor.authorWeiser, Peter
dc.contributor.authorAppel, Michael C.
dc.contributor.authorGreiner, Dale L.
dc.contributor.authorMordes, John P.
dc.contributor.authorRossini, Aldo A.
dc.date2022-08-11T08:10:01.000
dc.date.accessioned2022-08-23T16:52:21Z
dc.date.available2022-08-23T16:52:21Z
dc.date.issued2001-05-04
dc.date.submitted2008-07-09
dc.identifier.citation<p>Diabetes. 2001 May;50(5):972-9.</p>
dc.identifier.issn0012-1797 (Print)
dc.identifier.pmid11334440
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42035
dc.description.abstractThymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes would be present in long-term ATOCs but could be rendered nondiabetogenic by co-culture with appropriate antigens. We observed that cells recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14 days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with polyinosinic: polycytidylic acid and a monoclonal antibody to preclude development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the presence of BBDR thyrocytes had no effect on the ability of recovered cells to induce diabetes in 70-80% of adoptive recipients. In contrast, co-culture in the presence of islets prevented transfer of diabetes, on average, in >90% of recipients. Fresh islets, frozen islets, and islets pretreated with streptozotocin to deplete insulin were equally effective in preventing diabetes, but none prevented insulitis in nondiabetic recipients. Co-culture in the presence of islets was not associated with detectable alterations in phenotype or in the secretion of gamma-interferon or interleukin-4, either in cultures or in cells recovered from adoptive recipients. We conclude that islet antigens involved in the initiation of autoimmune diabetes in BB rats may be absent or deficient in BB rat thymi. Exposure of ATOCs to exogenous islets may lead to deletion or anergy of diabetogenic T-cells or to the positive selection of regulatory T-cells.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11334440&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.2337/diabetes.50.5.972
dc.subjectAdoptive Transfer
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectCoculture Techniques
dc.subjectDiabetes Mellitus, Type 1
dc.subjectImmunity, Natural
dc.subjectImmunophenotyping
dc.subjectInterferon Type II
dc.subjectInterleukin-4
dc.subjectIslets of Langerhans
dc.subjectLymph Nodes
dc.subjectLymphocyte Transfusion
dc.subjectRats
dc.subjectRats, Inbred BB
dc.subjectRats, Nude
dc.subjectReceptors, Transferrin
dc.subjectSpleen
dc.subjectT-Lymphocytes
dc.subjectThymus Gland
dc.subjectTime Factors
dc.subjectTransplantation, Homologous
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleBB rat thymocytes cultured in the presence of islets lose their ability to transfer autoimmune diabetes
dc.typeJournal Article
dc.source.journaltitleDiabetes
dc.source.volume50
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/484
dc.identifier.contextkey544966
html.description.abstract<p>Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes would be present in long-term ATOCs but could be rendered nondiabetogenic by co-culture with appropriate antigens. We observed that cells recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14 days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with polyinosinic: polycytidylic acid and a monoclonal antibody to preclude development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the presence of BBDR thyrocytes had no effect on the ability of recovered cells to induce diabetes in 70-80% of adoptive recipients. In contrast, co-culture in the presence of islets prevented transfer of diabetes, on average, in >90% of recipients. Fresh islets, frozen islets, and islets pretreated with streptozotocin to deplete insulin were equally effective in preventing diabetes, but none prevented insulitis in nondiabetic recipients. Co-culture in the presence of islets was not associated with detectable alterations in phenotype or in the secretion of gamma-interferon or interleukin-4, either in cultures or in cells recovered from adoptive recipients. We conclude that islet antigens involved in the initiation of autoimmune diabetes in BB rats may be absent or deficient in BB rat thymi. Exposure of ATOCs to exogenous islets may lead to deletion or anergy of diabetogenic T-cells or to the positive selection of regulatory T-cells.</p>
dc.identifier.submissionpathoapubs/484
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.source.pages972-9


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