[IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis].
OBJECTIVE
To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).


METHODS
EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.


RESULTS
EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.


CONCLUSIONS
Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.
Li
Wei-Min
WM
Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Liu
Wei
W
Gao
Cheng
C
Zhou
Bao-Guo
BG
Wang
Zheng
Z
Zhang
Rui-Hong
RH
Kong
Yi-Hui
YH
Li
Yue
Y
Han
Wei
W
Gan
Run-Tao
RT
Xue
Hong-Jie
HJ
Geng
Jian-Qiang
JQ
Yang
Shu-Sen
SS
Shao
Qun
Q
Zhang
Mei
M
D000818:Animals; D030801:Animals, Genetically Modified; D001327:Autoimmune Diseases / Q000276:immunology*; D001854:Bone Marrow Cells; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D015316:Genetic Therapy; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D009205:Myocarditis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
D016753:Interleukin-10