Experimental Study On CD4~+CD25~+ Regulatory T Cells In Peripheral Blood Of Patients With Rheumatic Heart Disease

Objective: Rheumatic Heart Disease(RHD), the pathogens of which is extremely complex and involves many cellular and molecular mechanisms, is a common human autoimmune disease. CD4+CD25+ regulatory T cells(Tregs) are primarily engaged in the maintenance of immunological self-tolerance and homeostasis by suppressing aberrant or excessive immune responses of autoreactive T cells. This work was aimed to evaluate the possible altered function of peripheral Tregs and the expression of FOXP3. To explore the relationship between Foxp3 gene and Treg function in molecular mechanism of RHD. Methods: Peripheral blood was collected from 40 patients with RHD and 20 healthy control subjects that were consecutively enrolled from November2014 to July 2015 in the Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University. All patients were diagnosed by clinical symptoms, history of rheumatic fever and echocardiography. The proportion of CD4+CD25+Tregs and CD4+CD25+Foxp3+ T cells among the total CD4+T-cell population were analyzed by means of flow cytometry. Foxp3 expression was evaluated through quantitative real time PCR and western blotting. Plasma concentrations of cytokines IL-10, TGF-β1 were measured using Cytometricbead array(CBA). Resuils: In RHD patient group, the number of peripheral CD4+CD25+Tregs accounted for the proportion of the number of CD4+T-cell was significantly lower than those in Control group. RHD group subjects had significantly decreased variability in the percentage of CD4+CD25+Foxp3+T cells compared with those in Control subjects. Moreover, the percentage of CD4+CD25+Foxp3+/CD4+ T cells correlated with that of CD4+CD25+Treg/CD4+T cells(r=0.9442; p<0.0001) in RHD patients. A comparison of Foxp3 mRNA and protein expression revealed significantly lower levels in patients with RHD than control subjects. Plasma concentrations of cytokines IL-10, TGF-β1 were decreased in RHD patients compared with those of the control subjects.Conclusions: Our data demonstrate that decreased frequency of Tregs and reduction in Foxp3 expression, suggestive of decreased peripheral immune tolerance, could be a potential pathogenesis of RHD resulted from the impaired immunoregulation by Tregs.