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© 2011 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Objective

Animal studies suggest that regulatory T (Treg) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of Treg cells in patients with chronic heart failure (CHF). However, the mechanisms behind Treg-cell defects remained unknown. We here sought to elucidate the mechanism of Treg-cell defects in CHF patients.

Methods and Results

We performed flow cytometry analysis and demonstrated reduced numbers of peripheral blood CD4+CD25+FOXP3+CD45RO−CD45RA+ naïve Treg (nTreg) cells and CD4+CD25+FOXP3+CD45RO+CD45RA− memory Treg (mTreg) cells in CHF patients as compared with non-CHF controls. Moreover, the nTreg/mTreg ratio (p<0.01), CD4+CD25+FOXP3+CD45RO− CD45RA+CD31+ recent thymic emigrant Treg cell (RTE-Treg) frequency (p<0.01), and T-cell receptor excision circle levels in Treg cells (p<0.01) were lower in CHF patients than in non-CHF controls. Combined annexin-V and 7-AAD staining showed that peripheral Treg cells from CHF patients exhibited increased spontaneous apoptosis and were more prone to interleukin (IL)-2 deprivation- and CD95 ligand-mediated apoptosis than those from non-CHF individuals. Furthermore, analyses by both flow cytometry and real-time polymerase chain reaction showed that Treg-cell frequency in the mediastinal lymph nodes or Foxp3 expression in hearts of CHF patients was no higher than that of the 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.

Details

Title
Impaired Thymic Export and Apoptosis Contribute to Regulatory T-Cell Defects in Patients with Chronic Heart Failure
Author
Ting-Ting, Tang; Zheng-Feng, Zhu; Wang, Jun; Wen-Cai, Zhang; Tu, Xin; Xiao, Hong; Xin-Ling, Du; Jia-Hong, Xia; Nian-Guo, Dong; Su, Wei; Ni Xia; Xing-Xing, Yan; Shao-Fang Nie; Liu, Juan; Su-Feng, Zhou; Yao, Rui; Jiang-Jiao, Xie; Jevallee, Harish; Wang, Xiang; Meng-Yang, Liao; Guo-Ping, Shi; Fu, Michael; Yu-Hua, Liao; Cheng, Xiang
First page
e24272
Section
Research Article
Publication year
2011
Publication date
Sep 2011
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1308584866
Copyright
© 2011 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.