| Objective:Our previous research has confirmed that regulatory T(Treg) cells from patients with chronic heart failure (CHF) were defective in their number and function compared to non-CHF controls. However, the mechanism is still not clear. This study aimed to find the mechanisms for the Treg defects in CHF patients.Methods:52CHF patients (including20ischemic heart failure (IHF) patients and32non-ischemic heart failure (NTHF) patients) and43non-CHF controls were included in the study. Peripheral blood samples were obtained and PMBCs were isolated by density gradient centrifugation. The frequencies of CD4+CD25+FOXP3+CD45RO-CD45RA+naive Treg(nTreg) cells, CD4+CD25+FOXP3+CD45RO+CD45RA-memory Treg(mTreg) cells and CD4+CD25+FOXP3+CD45ROCD45RA+CD31+recent thymic emigrant Treg (RTE-Treg) cells were determined by flow cytometry. Treg cells were purified by magnetic sorting and the level of T-cell receptor excision circles (TRECs) in Treg cells was analyzed by real-time polymerase chain reaction (RT-PCR). The spontaneous and induced apoptosis of Treg cells were detected by combined annexin-V and7-AAD co-staining. Plasma sCD95ligand was determined by enzyme linked immunosorbent assay (ELISA).Results:We demonstrated reduced numbers of peripheral blood nTreg cells and mTreg cells in CHF patients as compared with non-CHF controls.Moreover, the nTreg/mTreg ratio (p<0.01), RTE-Treg cells frequency (p<0.01), and TREC levels in Treg cells (p<0.01) were lower in CHF patients than in non-CHF controls. Peripheral Treg cells from CHF patients exhibited increased spontaneous apoptosis and were more prone to interleukin (IL)-2deprivation-and CD95ligand-mediated apoptosis than those from non-CHF individuals. We detected significantly higher plasma levels of soluble CD95L in CHF patients than in non-CHF controls.Conclusion:Our data suggested that the Treg-cell defects of CHF patients were likely caused by decreased thymic output of nascent Treg cells and increased susceptibility to apoptosis in the periphery. |
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