Effect of blockage of costimulatory signal on murine abortion-prone model.
BACKGROUND
Inhibition of the key costimulatory signals results in T cell anergy, indicating the alloantigen-specific immunologic unresponsiveness. In this study, the effect of blockage of costimulatory signal CD(86) on murine abortion-prone model was studied.


METHODS
Thirty CBA/J female mice cohabitated with DBA/2 male or BALB/c male mice were investigated. CBA/J x DBA/2 matings were used as the abortion-prone model, and CBA/J x BALB/c matings were used as the normal pregnant model. The abortion-prone models were divided into experimental and control groups, and the normal pregnant models were set as a normal group (10 mice in each group). The mice in the experimental group were treated with anti-mouse CD(86) monoclonal antibody (mAb) (100 microg) on day 4.5 of gestation, while the controls received irrelevant-isotype matched rat IgG(2b). As for the normal group, nothing was given to the mice. The mice were killed on day 13.5 of gestation, embryo resorption rate and the expression of transforming growth factor beta(1) (TGF-beta(1)), plasminogen activator inhibitor 1 (PAI-1), and matrix metalloproteinase 9 (MMP-9) were detected. Then the data were analyzed by Chi-square test and Fisher's exact test.


RESULTS
The embryo resorption rate in the experimental (8.2%) and normal groups (7.7%) was significantly lower than that of the control (23.5%, P < 0.05). No significant difference was detected between the experimental and normal groups (P > 0.05). The positive expression rates of TGF-beta(1) and PAI-1 proteins in the experimental and normal groups were significantly higher than those in the control group (P < 0.05). The positive expression rate of MMP-9 protein in the experimental and normal groups was significantly lower than that in the control group (P < 0.05). No significant difference in the positive expression rates of the three proteins was detected between the experimental and normal groups (P > 0.05).


CONCLUSIONS
Blockage of costimulatory signal CD(86) at early pregnancy can treat uncertain recurrent spontaneous abortion by stimulating the expression of TGF-beta(1), MMP-9 and PAI-1 and reducing the embryo resorption rate.
Zhao
Fu-Xi
FX
Laboratory of Pathogenic Organism and Immunology, Medical College of Shanxi Datong University, Datong 037008, China. dtyzfx@163.com
Zhang
Yuan-Yuan
YY
Liu
Run-Hua
RH
Li
Shuan-Ming
SM
D000026:Abortion, Habitual / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D051940:B7-2 Antigen / Q000276:immunology* / Q000502:physiology; D020964:Embryo Loss / Q000517:prevention & control; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011247:Pregnancy; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000032:analysis
D000911:Antibodies, Monoclonal; D051940:B7-2 Antigen; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; D020780:Matrix Metalloproteinase 9