IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis.
- Author:
Wei-Min LI
1
;
Wei LIU
;
Cheng GAO
;
Bao-Guo ZHOU
;
Zheng WANG
;
Rui-Hong ZHANG
;
Yi-Hui KONG
;
Yue LI
;
Wei HAN
;
Run-Tao GAN
;
Hong-Jie XUE
;
Jian-Qiang GENG
;
Shu-Sen YANG
;
Qun SHAO
;
Mei ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Genetically Modified; Autoimmune Diseases; immunology; Bone Marrow Cells; Cell Line; Dendritic Cells; immunology; Genetic Therapy; Immune Tolerance; Interleukin-10; genetics; immunology; Myocarditis; immunology; Rats; Rats, Inbred Lew
- From: Chinese Journal of Cardiology 2006;34(8):703-707
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).
METHODSEAM 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.
RESULTSEAM 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.
CONCLUSIONTreatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.