Mouse bone marrow derived mesenchymal stem cells suppress lymphocyte proliferation through co-Inhibitor B7-H1 upregulated by IFN-γ
10.3760/cma.j.issn.0254-5101.2009.04.014
- VernacularTitle:IFN-γ经共抑制分子B7-H1正向调控小鼠骨髓间充质干细胞免疫抑制的研究
- Author:
Huiming SHENG
;
Hongyu HUANG
;
Yunyu WEI
;
Ying WANG
;
Li WANG
;
Baihua SHEN
;
Ningli LI
- Publication Type:Journal Article
- Keywords:
Mesenchymal stem cells;
Immunosuppression;
B7-H1;
IFN-γ
- From:
Chinese Journal of Microbiology and Immunology
2009;29(4):345-350
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanism of mesenchymal stem cells immunosupression lym- phocyte proliferation via B7-H1/PD-1 pathway upregnlated by IFN-γ. Methods Bone marrow derived mes-enchymal stem cells (MSC) were isolated and purified by repeat adherent passage and detected them multi-potential differentiation in conditioned culture medium. Then MSC were cocuhured with lymphocyte prolifera-tion and assayed the level using γ H-thymidine incorporation. Meanwhile, ELISA measured IFN-γ, TGF-β, TNF-α and IL-10 in the cocuhured supernaatant and analyzed variation of B7-H1 molecular profile in MSC by flow cytometry. At last siRNA technology was deploied to interfere B7-H1 expression and analyzed MSC im-munosuppression on lymphocyte proliferation. Results In vitro the isolated MSC become homogeneous spi-die-shaped adherent cells after five passages, and in conditioned culture medium they could differentiate into adipocytes, osteocytes and chondrocytes. In the eocuhure of MSC with mixed lymphocyte, lymphocyte prolif- eration stimulated by Con A or by anti-CD3/CD28 antibody. The cpm value of the proliferation detected by 3H thymidine incorporation showed MSC suppressed the proliferation significantly (P = 0. 0167, 0. 0081,<0.0001 ) and the suppressive potential in a dose-dependent fashion. In the coeuhured supernatant cyto-kine IFN-T and TNF-α were detected in high concentration, but TGF-β, IL-10 were undetected. Simultane- ously MSC in the coeuhure upregulated B7-H1 expression from basic expression 7% to higher than 70% ( P < 0.05 ). After interfere B7-H1 expression in MSC by specific siRNA, we detected lymphocyte proliferation and got higher cpm by 3H thymidine incorporation ( P < 0. 05 ). Conclusion MSC upregulated B7-H1 mo-lecular expression upon the stimuli of IFN-γ, and through the B7-H1/PD-1 pathway mediated immunosu-pression on lymphocyte proliferation.
