TNF blockade abrogates the induction of T cell‐dependent humoral responses in an allotransplantation model

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: anti‐;    TNF;    alloantibodies;    rejection;    graft survival;   

DOI  :  10.1189/jlb.0710392

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TNFblockademodulatesmanyaspectsoftheimmuneresponseandiscommonlyusedinawidearrayofimmune‐mediatedinflammatorydiseases.Asanti‐TNFinducesanti‐dsDNAIgMantibodiesbutnototherantinuclearreactivitiesinhumanarthritis,weinvestigatedheretheeffectofTNFblockadeontheinductionofTDhumoralresponsesusingcardiacallograftandxenograftmodels.Asingleinjectionofananti‐ratTNFantibodyinLEW.1ArecipientsgraftedwithcongenicLEW.1WheartsalmostcompletelyabrogatedtheinductionofIgMandIgGalloantibodies.ThiswasassociatedwithdecreasedIgdepositionandleukocyteinfiltrationinthegraftatDay5.TNFblockadedidnotaffectgerminal‐centerformationinthespleenorexpressionofTh1/Th2cytokines,costimulatoryandregulatorymolecules,andTLRsinspleenandgraftoftherecipientanimals.Clinically,theabrogationoftheinductionofthealloantibodieswasassociatedwithamarkedprolongationofgraftsurvival.Incontrast,anti‐TNFdidnotalteracutexenograftrejectionmediatedbyTIantibodiesinahamster‐to‐ratmodel.Takentogether,thesedataindicatethatTNFblockadeabrogatestheinductionofTDhumoralresponsesandaccordingly,mayhaveabeneficialeffectinantibody‐mediatedinflammatorypathologies...

【 授权许可】

CC BY