OX40 stimulation down-regulates the expression of Foxp3 in CD4+ CD25+ regulatory T cells
10.3760/cma.j.issn.0254-1785.2013.07.011
- VernacularTitle:OX40信号调节抑制小鼠CD4+CD25+调节性T淋巴细胞Foxp3的表达
- Author:
Dongxia MA
;
Lu WANG
;
Yue ZHAO
;
Ying XIANG
;
Bin LIU
- Publication Type:Journal Article
- Keywords:
T-Lymphocytes,regulatory;
CD4;
Costimulation;
Transplantation
- From:
Chinese Journal of Organ Transplantation
2013;34(7):424-427
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the regulatory effect of OX40 co-stimulatory signal on the expression of Foxp3 in inductive regulatory T cells (iTreg) in vitro.Method CD4+ CD25+ naive T cells were isolated from C57BL/6 mouse lymphocyte suspension by MASC CD4+ CD25+ regulatory T cell isolation kit.Inductive Tregs were generated by stimulation of naive T cells in the presence of transforming growth factor beta (TGFβ1),anti-CD3,anti-CD28 and IL-2.The regulatory effect on iTregs was shown by use of OX40 stimulation monoclonal antibody (OX86) or control antibody.Using flow cytometric analysis (FACS),we examined the antibody-based identification of Tregs surface markers CD4 and CD25,along with the intracellular activation marker FoxP3.Results The ratio of CD4+ CD25+ nTregs isolated from mouse lymphatic node was (5.0 ± 0.4)％ vs.(71.8 ± 13.4)％ of TGFβ1-driven iTregs.The ratio of CD4+ CD25+ Tregs was (80.0 ± 1.6) ％ in OX40 stimulation McAb group vs.(86.0 ± 1.4)％ in control antibody group.Furthermore,the expression of Foxp3 was (59.2 ± 0.7) ％ in OX40 stimulation McAb group vs.(70.0 ± 0.8) ％ in control antibody group (P＜0.05).Conclusion TGFβ1-dependent protocol may induce the conversion of naive CD4+ T cells into CD25+ Foxp3+ iTregs.OX40 stimulation can down-regulate the expression of Foxp3 in CD4+ CD25 + iTreg significantly.Thus OX40 molecular may become an attractive target in Tregs-induced transplant tolerance.Further study should be performed to increase the suppressive activity of iTregs through blockade of OX40 signal.
