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dc.contributor.authorSeung, Edward
dc.contributor.authorIwakoshi, Neal N.
dc.contributor.authorWoda, Bruce A.
dc.contributor.authorMarkees, Thomas G.
dc.contributor.authorMordes, John P.
dc.contributor.authorRossini, Aldo A.
dc.contributor.authorGreiner, Dale L.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:42:09Z
dc.date.available2022-08-23T16:42:09Z
dc.date.issued2000-03-09
dc.date.submitted2008-04-14
dc.identifier.citationBlood. 2000 Mar 15;95(6):2175-82.
dc.identifier.issn0006-4971 (Print)
dc.identifier.pmid10706892
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40033
dc.description.abstractWe describe a tolerance-based stem cell transplantation protocol that combines sublethal radiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, we established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. The percentage of donor-origin mononuclear cells in recipients was more than 99%. In addition, all chimeric mice treated with anti-CD154 antibody remained free of graft-versus-host disease (GVHD) and accepted donor-origin but not third-party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. We conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sublethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as 2 injections of anti-CD154 antibody. We also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts. (Blood. 2000;95:2175-2182)
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10706892&dopt=Abstract">Link to article in PubMed</a>
dc.subjectAnimals
dc.subject*Autoimmunity
dc.subjectBone Marrow
dc.subjectCD40 Ligand
dc.subjectDiabetes Mellitus, Experimental
dc.subjectFemale
dc.subject*Graft Survival
dc.subjectGraft vs Host Disease
dc.subjectHyperglycemia
dc.subjectImmune Tolerance
dc.subjectIslets of Langerhans
dc.subject*Islets of Langerhans Transplantation
dc.subjectMale
dc.subjectMembrane Glycoproteins
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMice, Inbred C57BL
dc.subjectMice, Inbred CBA
dc.subjectMice, Inbred NOD
dc.subjectRecurrence
dc.subjectSkin Transplantation
dc.subjectTime Factors
dc.subject*Transplantation Chimera
dc.subjectTransplantation Conditioning
dc.subject*Transplantation, Homologous
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectImmunology and Infectious Disease
dc.subjectMedical Immunology
dc.subjectMedical Pathology
dc.subjectVirology
dc.titleAllogeneic hematopoietic chimerism in mice treated with sublethal myeloablation and anti-CD154 antibody: absence of graft-versus-host disease, induction of skin allograft tolerance, and prevention of recurrent autoimmunity in islet-allografted NOD/Lt mice
dc.typeJournal Article
dc.source.journaltitleBlood
dc.source.volume95
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1283&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/284
dc.identifier.contextkey489621
refterms.dateFOA2022-08-23T16:42:09Z
html.description.abstract<p>We describe a tolerance-based stem cell transplantation protocol that combines sublethal radiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, we established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. The percentage of donor-origin mononuclear cells in recipients was more than 99%. In addition, all chimeric mice treated with anti-CD154 antibody remained free of graft-versus-host disease (GVHD) and accepted donor-origin but not third-party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. We conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sublethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as 2 injections of anti-CD154 antibody. We also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts. (Blood. 2000;95:2175-2182)</p>
dc.identifier.submissionpathoapubs/284
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentProgram in Immunology and Virology
dc.source.pages2175-82


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