CD4~+CD25~+Foxp3~+ Regulatory T Cells In Patients With Chronic Heart Failure

PartⅠDown-regulation of CD4+CD25+Foxp3+ regulatory T cells in patients with chronic heart failureObjective: Mounting evidence demonstrates that immune activation may play critical roles in pathogensis and progression of chronic heart failure (CHF). CD4+CD25+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells with immunomodulatory effect. The purpose of the study is to detect the alteration of frequencies and function of peripheral blood CD4+CD25+Foxp3+ regulatory T cells from patients with chronic heart failure.Method: Peripheral blood samples were collected from 48 patients with CHF, of which 25 patients with ischemic heart disease (IHD group), 23 non-ischemic heart disease (NIHD group), and 20 healthy donors (Control group). Peripheral frequencies of CD4+CD25+ Foxp3+ Tregs were evaluated by flow cytometric analysis, FOXP3 mRNA in peripheral blood monocyte cells were determined by real-time RT-PCR, levels of plasma TGF-β1 were detected by ELISA.Result: Peripheral frequencies of CD4+CD25+Foxp3+Treg cells were significantly decreased in patients with CHF compared with in healthy donors (IHD group vs Control group 1.41±0.71% vs 5.59±1.73%, P<0.01; NIHD group vs Control group 1.24±0.54% vs 5.59±1.73%, P<0.01), which corresponded to data that lower levels of expression of FOXP3 mRNA and plasma TGF-β1. However, there is no significant difference in CD4+CD25+Foxp3+ Treg numbers between IHD group and NIHD group.Conclusion: In patients with CHF, peripheral CD4+CD25+Foxp3+Treg numbers are reduced, and their functional properties compromised. This alteration of CD4+CD25+ Foxp3+ Treg may be assiociated with the process of immune activation of CHF.PartⅡStatins modulate CD4+CD25+Foxp3+ regulatory T cells in patients with chronic heart failure in vitroObjective: Considerable evidence suggests that the immunomodulatory property of statins may contribute to chronic heart failure. CD4+CD25+ regulatory T cells (Treg) have a key role in prevention of various inflammatory and autoimmune disorders. The purpose of the study was to determine the effects of statins on CD4+CD25+Foxp3+ regulatory T cells from peripheral blood in patients with CHF in vitro.Methods:Blood samples were collected from 10 patients with CHF secondary to non-ischemic heart diseases. Peripheral blood monocyte cells were cultured with 1, 5 and 10μM atorvastatin or 1, 2.5 and 5μM rosuvastatin, controlled with blank, and collected after 96h. Frequencies of CD4+CD25+T cells and CD4+CD25+Foxp3+Treg were evaluated by flow cytometric analysis, FOXP3 mRNA in peripheral blood monocyte cells were determined by real time RT-PCR.Results:Frequencies of CD4+CD25+ T cells and CD4+CD25+Foxp3+ Tregs in patients with CHF were significantly increased in lipophilic atorvastatin treatment group ,but not hydrophilic rosuvastatin treatment group, compared with those in control group (P<0.01), which corresponded to data with higher levels of expression of FOXP3 mRNA.Conclusion: Lipophilic atorvastatin can significantly increase numbers of CD4+CD25+ Foxp3+ Tregs in vitro, which may contribute to the immune hemeostasis of CHF.