Study On The Expression Of Peripheral Costimulatory Molecule And The Change In Estrogen Levels Of Perimenopausal And Postmenopausal Women

Objective To analyze the CD28,CTLA-4,PD-1and PD-L1expression on peripheralblood mononuclear cells and T cells of perimenopausal and postmenopausal women. Inattempt to investigate the relevance and significance of the immune function and changesin serum estrogen.Methods The mRNA expression of CD28,CTLA-4, PD-1and PD-L1on peripheralblood mononuclear cells were detected by Taqman probe real-time quantitative PCR, andthe levels of CD28,CTLA-4and PD-1on T cells and T lymphocyte subsets weredetermined by Flow Cytometry, including70cases perimenopausal,40casespostmenopausal women and30cases normal control(NC). And estradiol (E2),progesterone(Pg),follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in serum forcomprehensive analysis.Results There were statistically significant difference with the expression level ofCD28mRNA(F=5.729, P <0.05) in different group,with the highest expression level inthe postmenopausal groups (6.84±0.56) and with the lowest in healthy control group(6.37±0.54). There were statistically significant difference with the expression level ofCTLA-4mRNA (F=28.594, P <0.01) in different groups, with the highest expression levelin the postmenopausal group(6.80±1.01)and with the lowest in perimenopausal group(5.32±0.90). There were statistically significant difference with the expression level ofPD-1mRNA (F=12.222, P <0.01) in different group,with the highest expression level inthe postmenopausal group (5.46±0.68) and with the lowest in healthy control group(4.43±0.89). There were statistically significant difference with the expression level of PD-L1mRNA (F=24.825, P <0.01) in different groups,with the highest expression level in thepostmenopausal groups (5.07±0.85) and with the lowest in healthy control group (3.82±0.68).There were significant positive correlation of the expression levels of PD-1mRNA and the level of E2(r=-0.207,P=0.031), and there were significant negative correlation ofthe expression level of PD-L1mRNAand the level of E2（r=-0.353,P<0.001）.There werestatistically significant difference with the expression levels of CD3+and CD4+Tcells andthe ratio of CD4+/CD8+in the three groups. All of the levels in perimenopausal andpostmenopausal groups were lower than NC. There were statistically significant differencewith the expression levels of CD28on T cells, and in the perimenopausal andpostmenopausal groups were significantly lower than NC. The ratio of CD28+/CTLA-4+inthe postmenopausal group was much lower than perimenopausal group and NC. Therewere statistically significant difference with the expression levels of PD-1on T cells, andin the perimenopausal and postmenopausal groups were significantly lower than NC. Therewere significant positive correlation of the expression levels of CD3+and CD4+Tcells andthe level of E2(r=0.256,0.246.P=0.007,0.005).There were significant positive correlationof the expression levels of CD3+and CD4+T cells and the age(r=-0.387,-0.456.P<0.001).PD-1on CD4and CD8T cells show significant positive correlation with the level ofE2(r=0.550,0.554.P<0.001).Conclusion1. The relative expression and absolute value of CD3+,CD4+and CD8+T cells wereall decreased in the perimenopausal and postmenopausal women. It was implied that thewomen exist T cell immune dysfunction.2. The mRNA expression of CD28,CTLA-4, PD-1and PD-L1on peripheral bloodmononuclear cells were shown disorderd. The transcriptional change provides basicinformation for further study the interaction of co-stimulatory molecules, estrogen andimmune function.3. There was a significant positive correlation between the amount of CD3+T, CD4+T,PD-1and the level of E2. It implied that estrogen may be regulating the expression ofPD-1molecule and reduced perimenopausal and postmenopausal women immunefunction.