Intervention mechanism of a dual analogue on Foxp3 and CD4 + CD25 + regulatory T cells in passive transferred myasthenia gravis in young mice
10.3760/cma.j.issn.2095-428X.2013.14.020
- VernacularTitle:双类似物对重症肌无力幼鼠Foxp3+CD4+CD25+Tregs的作用机制
- Author:
Xiu-Li WEI
1
;
Zhi HUANG
Author Information
1. 南阳市中心医院
- Keywords:
Myasthenia gravis;
Nasal tolerance;
Dual analogue;
Regulatory T cell;
Foxp3
- From:
Chinese Journal of Applied Clinical Pediatrics
2013;28(14):1108-1111
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207),on the mouse model of passive transferred myasthenia gravis(PTMG) and the underlying mechanism,and to explore the cell immunologic intervention function and regulatory mechanism of Foxp3 on nasal tolerance with Lys262-Ala207 on PTMG.Methods Mouse model of PTMG was established by intraperitoneal injection of mAb35.Twentyfour C57BL/6 young female mice were divided equally into 3 groups:tolerance group (group T),model control group (group MC)and normal control group(group C).Lys262-Ala207 or PBS was given nasally before 10 days of immunization for 10 days.Clinical symptoms were evaluated after immunization.Serum level of acetylcholine receptor antibody IgG was detected by using ELISA.Levels of CD4 + CD25 + T cells and Foxp3 + CD4 + CD25 + Tregs in spleen cells were measured by flow cytometry.Expression of Foxp3 mRNA in spleen cells was detected by real-time fluorescent quantitative polymerase chain reaction.Serum levels of IL-2 and IFN-γ were detected by ELISA.Results 1.Compared with group MC,the clinical symptoms were improved in mice of group T,but which did not return to normal.2.The positive rate of the repetitive nerve stimulation test in group T was significantly lower than that in group MC,and the serum levels of AChR-Ab IgG in group T decreased compared with that in group MC,the differences were significant.Both the test items in group T were higher than those in group C,the differences were significant (all P ＜ 0.05).3.The ratio of CD4 + CD25 + T cells and CD4 + T cells in group T increased compared with that in group MC,the differences were significant(all P ＜0.01,0.05) ;The ratio of Foxp3 + CD4 + CD25 + Tregs and CD4 + CD25 + T cells in group T were higher than those in group MC,the differences were significant(all P ＜ 0.01) ; The level of Foxp3 mRNA in spleen cells in group T was higher than that in group MC,the difference was significant(P ＜0.05) ;All the test items in group T were lower than those in group C,but the differences were significant (P ＜ 0.05).The serum levels of IL-2 and IFN-γin group T were lower than those in group MC,the serum levels of IL-2 and IFN-γin group T were also higher than those in group C,the differences were significant (all P ＜ 0.05,0.01).Conclusions Nasal administration with Lys262-Ala207 has preventive effects on PTMG in young mice.One of prophylactic mechanisms of dual analogues may be due to up-regulation of Foxp3 mRNA expression.Foxp3 has the possibility to be a target gene for MG treatment.
