Anti-CD154 mAb and Rapamycin Induce T Regulatory Cell Mediated Tolerance in Rat-to-Mouse Islet Transplantation 英文参考文献.docVIP
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Anti-CD154 mAb and Rapamycin Induce T Regulatory Cell Mediated Tolerance in Rat-to-Mouse Islet Transplantation 英文参考文献
Anti-CD154mAbandRapamycinInduceTRegulatory
CellMediatedToleranceinRat-to-MouseIslet
Transplantation
YannickD.Muller1,2*.,GangMai1,3.,PhilippeMorel1,Ve′roniqueSerre-Beinier1,CarmenGonelle-
Gispert1,GisellaPugaYung2,DrissEhirchiou2,Jean-ChristopheWyss4,SindaBigenzahn5,MagaliIrla6,
ChristophHeusser7,De′laGolshayan4,Jo¨rgD.Seebach2,ThomasWekerle5,LeoH.Bu¨hler1
1Surgical Research Unit, Department of Surgery, University Hospital Geneva, Geneva, Switzerland, 2Service of Clinical Immunology and Allergology, Department of
Internal Medicine, University Hospital and Medical Faculty, Geneva, Switzerland, 3Hepato- Bilio-Pancreatic Department, West China Hospital, Si Chuan University,
Chengdu,SiChuan,People’sRepublicofChina,4TransplantationImmunopathologyLaboratory,DepartmentofMedicine,UniversityofLausanne,Lausanne,Switzerland,
5DivisionofTransplantation,DepartmentofSurgery,ViennaGeneralHospital,MedicalUniversityofVienna,Vienna,Austria,6UniversityofGenevaMedicalSchool,CMU,
Geneva,Switzerland,7NovartisInstitutesforBiomedicalResearch,Basel,Switzerland
Abstract
Background:Anti-CD154(MR1)monoclonalantibody(mAb)andrapamycin(RAPA)treatmentbothimprovesurvivalofrat-
to-mouseisletxenograft.ThepresentstudyinvestigatedtheeffectofcombinedRAPA/MR1treatmentonrat-to-mouseislet
xenograftsurvivalandanalyzedtheroleofCD4 CD25 Foxp3+Tregulatorycells(Treg)intheinductionandmaintenanceof
+
+
theensuingtolerance.
Methodology/PrincipalFindings:C57BL/6miceweretreatedwithMR1/RAPAandreceivedadditionalmonoclonalanti-IL2
mAborantiCD25mAbeitherearly(0–28d)orlate(100–128d)post-transplantation.Tregwerecharacterisedintheblood,
spleen, draining lymph nodes and within the graft of tolerant and rejecting mice by flow cytometry and
immunohistochemistry.FourteendaysofRAPA/MR1combinationtherapyallowedindefiniteisletgraftsurvivalin.80%of
themice.Additionaladministrationofanti-IL-2mAbordepletinganti-CD25mAbatthetimeoftransplantationresultedin
rejection(100%and89%respectively),whereasadministrationat100daysposttr
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