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dc.contributor.authorIwakoshi, Neal N.
dc.contributor.authorMordes, John P.
dc.contributor.authorMarkees, Thomas G.
dc.contributor.authorPhillips, Nancy E.
dc.contributor.authorRossini, Aldo A.
dc.contributor.authorGreiner, Dale L.
dc.date2022-08-11T08:08:59.000
dc.date.accessioned2022-08-23T16:14:39Z
dc.date.available2022-08-23T16:14:39Z
dc.date.issued1999-12-22
dc.date.submitted2008-10-09
dc.identifier.citation<p>J Immunol. 2000 Jan 1;164(1):512-21.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.164.1.512
dc.identifier.pmid10605049
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33910
dc.description.abstractA two-element protocol consisting of one donor-specific transfusion (DST) plus a brief course of anti-CD154 mAb greatly prolongs the survival of murine islet, skin, and cardiac allografts. To study the mechanism of allograft survival, we determined the fate of tracer populations of alloreactive transgenic CD8+ T cells in a normal microenvironment. We observed that DST plus anti-CD154 mAb prolonged allograft survival and deleted alloreactive transgenic CD8+ T cells. Neither component alone did so. Skin allograft survival was also prolonged in normal recipients treated with anti-CD154 mAb plus a depleting anti-CD8 mAb and in C57BL/6-CD8 knockout mice treated with anti-CD154 mAb monotherapy. We conclude that, in the presence of anti-CD154 mAb, DST leads to an allotolerant state, in part by deleting alloreactive CD8+ T cells. Consistent with this conclusion, blockade of CTLA4, which is known to abrogate the effects of DST and anti-CD154 mAb, prevented the deletion of alloreactive transgenic CD8+ T cells. These results document for the first time that peripheral deletion of alloantigen-specific CD8+ T cells is an important mechanism through which allograft survival can be prolonged by costimulatory blockade. We propose a unifying mechanism to explain allograft prolongation by DST and blockade of costimulation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10605049&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.164.1.512
dc.subjectAnimals; Antibodies, Monoclonal; Antigens, CD; Antigens, CD40; Antigens, CD8; Antigens, Differentiation; *Blood Transfusion; CD40 Ligand; CD8-Positive T-Lymphocytes; Combined Modality Therapy; Epitopes, T-Lymphocyte; Female; Graft Survival; *Immunoconjugates; Immunophenotyping; Immunosuppressive Agents; Isoantigens; Ligands; Lymph Nodes; Lymphocyte Activation; Lymphocyte Count; *Lymphocyte Depletion; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Transgenic; Skin Transplantation; Thymectomy; Time Factors
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleTreatment of allograft recipients with donor-specific transfusion and anti-CD154 antibody leads to deletion of alloreactive CD8+ T cells and prolonged graft survival in a CTLA4-dependent manner
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume164
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/565
dc.identifier.contextkey646750
html.description.abstract<p>A two-element protocol consisting of one donor-specific transfusion (DST) plus a brief course of anti-CD154 mAb greatly prolongs the survival of murine islet, skin, and cardiac allografts. To study the mechanism of allograft survival, we determined the fate of tracer populations of alloreactive transgenic CD8+ T cells in a normal microenvironment. We observed that DST plus anti-CD154 mAb prolonged allograft survival and deleted alloreactive transgenic CD8+ T cells. Neither component alone did so. Skin allograft survival was also prolonged in normal recipients treated with anti-CD154 mAb plus a depleting anti-CD8 mAb and in C57BL/6-CD8 knockout mice treated with anti-CD154 mAb monotherapy. We conclude that, in the presence of anti-CD154 mAb, DST leads to an allotolerant state, in part by deleting alloreactive CD8+ T cells. Consistent with this conclusion, blockade of CTLA4, which is known to abrogate the effects of DST and anti-CD154 mAb, prevented the deletion of alloreactive transgenic CD8+ T cells. These results document for the first time that peripheral deletion of alloantigen-specific CD8+ T cells is an important mechanism through which allograft survival can be prolonged by costimulatory blockade. We propose a unifying mechanism to explain allograft prolongation by DST and blockade of costimulation.</p>
dc.identifier.submissionpathgsbs_sp/565
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.contributor.departmentProgram in Immunology and Virology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages512-21


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