Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the allograft protection induced by infusion of donor-specific splenic stromal cells  

作　　者：Li Liu Lihua Duan Min Gong Hong Dai Quan Gong Fang Zheng Zheng Tan Congyi Wang Feili Gong Min Fang 

机构地区：[1]Laboratory of Transplantation,Department of Immunology,Tongji Medical College of Huazhong University of Science and Technology,Wuhan,China [2]The Center for Biomedical Research,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China

出　　处：《Cellular & Molecular Immunology》2011年第1期31-40,共10页中国免疫学杂志（英文版）

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).

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 cytokines.In 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 cells.However,the precise mechanisms by which these SSCs exert their regulatory functions in vivo remain undefined.Furthermore,their possible contribution to the development of allograft transplantation tolerance has yet to be examined.Here,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 rejection.We show that intravenous SSC infusion prolonged murine skin allograft survival.The 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)-b.Moreover,we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs contribute to allograft protection by infusion of donor-specific SSCs.Our data suggest that donor-derived SSCs could be used as a therapeutic target to promote transplantation tolerance.

关 键 词：dendritic cell indoleamine 2 3-dioxygenase splenic stromal cell TRANSPLANTATION 

分 类 号：R73[医药卫生—肿瘤]