Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells
作者机构:Laboratory of TransplantationDepartment of ImmunologyTongji Medical College of Huazhong University of Science and TechnologyWuhanChina The Center for Biomedical ResearchTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
出 版 物:《Cellular & Molecular Immunology》 (中国免疫学杂志(英文版))
年 卷 期:2011年第8卷第1期
页 面:31-40页
核心收录:
学科分类:0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金:This work was supported by the National Natural Science Foundation of China(grants 30772039 and 81072440) the National Natural Science Foundation of China-Guangdong Province Union Grant(U0832003) the Ministry of Science and Technology of China(grant 2007CB512402)
主 题:dendritic cell indoleamine 2,3-dioxygenase splenic stromal cell transplantation
摘 要:It has been reported that splenic stromal cells(SSCs)are capable of directly supporting the development of CD11c ^(lo)CD45RB^(+) IL-10-producing dendritic cells(DCs)from lineage-negative c-kit^(+) progenitor cells in the absence of exogenous *** vitro,DCs that differentiate on stromal cells suppress mixed leukocyte reaction responses and induce primary alloreactive CD4^(+) T cells to differentiate into IL-10-producing Tr1 ***,the precise mechanisms by which these SSCs exert their regulatory functions in vivo remain ***,their possible contribution to the development of allograft transplantation tolerance has yet to be ***,we have used both murine skin and cardiac allograft transplantation models to explore whether in vivo alloresponses can be regulated by infusion with donor-derived SSCs and to investigate the possible mechanisms by which SSCs exert regulatory effects to prevent allograft *** show that intravenous SSC infusion prolonged murine skin allograft *** prolonged graft survival is associated with augmentation of the generation of regulatory DC subsets and CD4^(+) CD25^(+) Foxp3^(+) regulatory T cells(Tregs),as well as upregulation of the production of suppressive cytokines IL-10 and transforming growth factor(TGF)-***,we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs contribute to allograft protection by infusion of donor-specific *** data suggest that donor-derived SSCs could be used as a therapeutic target to promote transplantation tolerance.