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dc.contributor.authorD’Addio, Francesca
dc.contributor.authorBoenisch, Olaf
dc.contributor.authorMagee, Ciara N
dc.contributor.authorYeung, Melissa
dc.contributor.authorYuan, Xueli
dc.contributor.authorMfarrej, Bechara
dc.contributor.authorVergani, Andrea
dc.contributor.authorAnsari, Mohammed Javeed
dc.contributor.authorFiorina, Paolo
dc.contributor.authorNajafian, Nader
dc.date.accessioned2013-05-24T18:26:45Z
dc.date.issued2013
dc.identifier.citationD’Addio, Francesca, Olaf Boenisch, Ciara N. Magee, Melissa Y. Yeung, Xueli Yuan, Bechara Mfarrej, Andrea Vergani, Mohammed Javeed Ansari, Paolo Fiorina, and Nader Najafian. 2013. Prolonged, low-dose anti-thymocyte globulin, combined with CTLA4-Ig, promotes engraftment in a stringent transplant model. PLoS ONE 8(1): e53797.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10665228
dc.description.abstractBackground: Despite significant nephrotoxicity, calcineurin inhibitors (CNIs) remain the cornerstone of immunosuppression in solid organ transplantation. We, along with others, have reported tolerogenic properties of anti-thymocyte globulin (ATG, Thymoglobulin®), evinced by its ability both to spare Tregs from depletion in vivo and, when administered at low, non-depleting doses, to expand Tregs ex vivo. Clinical trials investigating B7/CD28 blockade (LEA29Y, Belatacept) in kidney transplant recipients have proven that the replacement of toxic CNI use is feasible in selected populations. Methods: Rabbit polyclonal anti-murine thymocyte globulin (mATG) was administered as induction and/or prolonged, low-dose therapy, in combination with CTLA4-Ig, in a stringent, fully MHC-mismatched murine skin transplant model to assess graft survival and mechanisms of action. Results: Prolonged, low-dose mATG, combined with CTLA4-Ig, effectively promotes engraftment in a stringent transplant model. Our data demonstrate that mATG achieves graft acceptance primarily by promoting Tregs, while CTLA4-Ig enhances mATG function by limiting activation of the effector T cell pool in the early stages of treatment, and by inhibiting production of anti-rabbit antibodies in the maintenance phase, thereby promoting regulation of alloreactivity. Conclusion: These data provide the rationale for development of novel, CNI-free clinical protocols in human transplant recipients.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0053797en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542267/pdf/en_US
dash.licenseLAA
dc.subjectMedicineen_US
dc.subjectClinical Immunologyen_US
dc.subjectImmune Cellsen_US
dc.subjectT Cellsen_US
dc.subjectImmunityen_US
dc.subjectImmune Activationen_US
dc.subjectImmune Suppressionen_US
dc.subjectImmune Toleranceen_US
dc.subjectImmunoregulationen_US
dc.subjectImmunotherapyen_US
dc.subjectImmunologic Techniquesen_US
dc.subjectImmunoassaysen_US
dc.subjectImmune Responseen_US
dc.subjectImmunomodulationen_US
dc.subjectSurgeryen_US
dc.subjectTransplant Surgeryen_US
dc.titleProlonged, Low-Dose Anti-Thymocyte Globulin, Combined with CTLA4-Ig, Promotes Engraftment in a Stringent Transplant Modelen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorNajafian, Nader
dc.date.available2013-05-24T18:26:45Z
dc.identifier.doi10.1371/journal.pone.0053797*
dash.contributor.affiliatedMagee, Ciara N
dash.contributor.affiliatedBoenisch, Olaf
dash.contributor.affiliatedYeung, Melissa
dash.contributor.affiliatedNajafian, Nader
dash.contributor.affiliatedVergani, Andrea
dash.contributor.affiliatedFiorina, Paolo


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