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Enhanced de novo alloantibody and antibody-mediated injury in rhesus macaques.

dc.contributor.author Gibby, Adriana C
dc.contributor.author Hennigar, RA
dc.contributor.author Iwakoshi, Neal N
dc.contributor.author Jenkins, JB
dc.contributor.author Knechtle, Stuart J
dc.contributor.author Kwun, J
dc.contributor.author Leopardi, F
dc.contributor.author Page, AJ
dc.contributor.author Page, EK
dc.contributor.author Song, M
dc.contributor.author Strobert, EA
dc.coverage.spatial United States
dc.date.accessioned 2015-05-16T11:55:43Z
dc.date.issued 2012-09
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/22776408
dc.identifier.uri http://hdl.handle.net/10161/10061
dc.description.abstract Chronic allograft rejection is a major impediment to long-term transplant success. Humoral immune responses to alloantigens are a growing clinical problem in transplantation, with mounting evidence associating alloantibodies with the development of chronic rejection. Nearly a third of transplant recipients develop de novo antibodies, for which no established therapies are effective at preventing or eliminating, highlighting the need for a nonhuman primate model of antibody-mediated rejection. In this report, we demonstrate that depletion using anti-CD3 immunotoxin (IT) combined with maintenance immunosuppression that included tacrolimus with or without alefacept reliably prolonged renal allograft survival in rhesus monkeys. In these animals, a preferential skewing toward CD4 repopulation and proliferation was observed, particularly with the addition of alefacept. Furthermore, alefacept-treated animals demonstrated increased alloantibody production (100%) and morphologic features of antibody-mediated injury. In vitro, alefacept was found to enhance CD4 effector memory T cell proliferation. In conclusion, alefacept administration after depletion and with tacrolimus promotes a CD4+memory T cell and alloantibody response, with morphologic changes reflecting antibody-mediated allograft injury. Early and consistent de novo alloantibody production with associated histological changes makes this nonhuman primate model an attractive candidate for evaluating targeted therapeutics.
dc.language eng
dc.relation.ispartof Am J Transplant
dc.relation.isversionof 10.1111/j.1600-6143.2012.04074.x
dc.subject Animals
dc.subject Graft Rejection
dc.subject Graft Survival
dc.subject Immunohistochemistry
dc.subject Immunologic Memory
dc.subject Immunosuppressive Agents
dc.subject Isoantibodies
dc.subject Lymphocyte Depletion
dc.subject Macaca mulatta
dc.subject Male
dc.title Enhanced de novo alloantibody and antibody-mediated injury in rhesus macaques.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/22776408
pubs.begin-page 2395
pubs.end-page 2405
pubs.issue 9
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Abdominal Transplant Surgery
pubs.publication-status Published
pubs.volume 12
dc.identifier.eissn 1600-6143


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