Regulatory T cells Suppress Pathogenic CD8(+)T cells in Primary Biliary Cirrhosis Mice Model
作者单位：中国科学技术大学
会议名称：《第九届全国免疫学学术大会》
会议日期：2014年
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学]
关 键 词：Primary Biliary Cirrhosis Regulatory T cells CD8 T cells Bone marrow transplantation Parabiosis
摘 要：Primary Biliary Cirrhosis(PBC)is a female dominant progressive autoimmune liver disease characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts.Mice with T cell-restricted expression of a dominant negative form of transforming growth factorβreceptor typeⅡ(dnTβRⅡ)spontaneously developed periductular aggregates in the liver.The precise relationship between the pathogenesis of PBC and regulatory T cells is poorly defined.Based on dnTpRII mice,it was determined that the frequency of Tregs didn’t change in lymph organs from dnTpRII;Foxp3mice,compared with wild type(Foxp3)mice.CD4Foxp3Tregs from dnTβRⅡmice up-regulated suppressive functional molecule,such as CD25,CTLA-4,GITR,ICOS,CD69,and highly expressed Th1 response or liver inflammation specific chemokine receptor CXCR3,meanwhile down-regulated CD62L(L-selectin),showed extremely activated phenotype.Besides,lacking of CD4T cells in dnTβRⅡ:CD4mice aggravated PBC-like symptom compared with dnTpRII mice.This data showed that in inflammatory milieu,regulatory T cells were over-activated.In the absence of CD4T cells,without the assistant from conventional CD4T cells and suppression from regulatory T cells,pathogenic T cells caused more severe liver inflammation.Moreover,WT,dnTpRII mice derived splenic Tregs and in vitro TGF-P induced Tregs(Ti-Tregs)showed obvious suppressive activity toward CD8T cells from dnTβRⅡmice.Our research provided evidence for the protective role of regulatory T cells in this PBC mice model.After parabioted with wild type mice,dnTβPⅡ:CD4mice showed almost no portal inflammation in liver and showed alleviated biliary disease.