Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought t...
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doaj-e6aab1f22f854e30a44d686b13aa584e2020-11-25T01:22:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2427210.1371/journal.pone.0024272Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.Ting-Ting TangZheng-Feng ZhuJun WangWen-Cai ZhangXin TuHong XiaoXin-Ling DuJia-Hong XiaNian-Guo DongWei SuNi XiaXin-Xin YanShao-Fang NieJuan LiuSu-Feng ZhouRui YaoJiang-Jiao XieHarish JevalleeXiang WangMeng-Yang LiaoGuo-Ping ShiMichael FuYu-Hua LiaoXiang ChengAnimal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.We performed flow cytometry analysis and demonstrated reduced numbers of peripheral blood CD4(+)CD25(+)FOXP3(+)CD45RO(-)CD45RA(+) naïve T(reg) (nT(reg)) cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+)CD45RA(-) memory T(reg) (mT(reg)) cells in CHF patients as compared with non-CHF controls. Moreover, the nT(reg)/mT(reg) ratio (p<0.01), CD4(+)CD25(+)FOXP3(+)CD45RO(-) CD45RA(+)CD31(+) recent thymic emigrant T(reg) cell (RTE-T(reg)) frequency (p<0.01), and T-cell receptor excision circle levels in T(reg) cells (p<0.01) were lower in CHF patients than in non-CHF controls. Combined annexin-V and 7-AAD staining showed that peripheral T(reg) 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 T(reg)-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.Our data suggested that the T(reg)-cell defects of CHF patients were likely caused by decreased thymic output of nascent T(reg) cells and increased susceptibility to apoptosis in the periphery.http://europepmc.org/articles/PMC3174174?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ting-Ting Tang Zheng-Feng Zhu Jun Wang Wen-Cai Zhang Xin Tu Hong Xiao Xin-Ling Du Jia-Hong Xia Nian-Guo Dong Wei Su Ni Xia Xin-Xin Yan Shao-Fang Nie Juan Liu Su-Feng Zhou Rui Yao Jiang-Jiao Xie Harish Jevallee Xiang Wang Meng-Yang Liao Guo-Ping Shi Michael Fu Yu-Hua Liao Xiang Cheng |
spellingShingle |
Ting-Ting Tang Zheng-Feng Zhu Jun Wang Wen-Cai Zhang Xin Tu Hong Xiao Xin-Ling Du Jia-Hong Xia Nian-Guo Dong Wei Su Ni Xia Xin-Xin Yan Shao-Fang Nie Juan Liu Su-Feng Zhou Rui Yao Jiang-Jiao Xie Harish Jevallee Xiang Wang Meng-Yang Liao Guo-Ping Shi Michael Fu Yu-Hua Liao Xiang Cheng Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure. PLoS ONE |
author_facet |
Ting-Ting Tang Zheng-Feng Zhu Jun Wang Wen-Cai Zhang Xin Tu Hong Xiao Xin-Ling Du Jia-Hong Xia Nian-Guo Dong Wei Su Ni Xia Xin-Xin Yan Shao-Fang Nie Juan Liu Su-Feng Zhou Rui Yao Jiang-Jiao Xie Harish Jevallee Xiang Wang Meng-Yang Liao Guo-Ping Shi Michael Fu Yu-Hua Liao Xiang Cheng |
author_sort |
Ting-Ting Tang |
title |
Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure. |
title_short |
Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure. |
title_full |
Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure. |
title_fullStr |
Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure. |
title_full_unstemmed |
Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure. |
title_sort |
impaired thymic export and apoptosis contribute to regulatory t-cell defects in patients with chronic heart failure. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.We performed flow cytometry analysis and demonstrated reduced numbers of peripheral blood CD4(+)CD25(+)FOXP3(+)CD45RO(-)CD45RA(+) naïve T(reg) (nT(reg)) cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+)CD45RA(-) memory T(reg) (mT(reg)) cells in CHF patients as compared with non-CHF controls. Moreover, the nT(reg)/mT(reg) ratio (p<0.01), CD4(+)CD25(+)FOXP3(+)CD45RO(-) CD45RA(+)CD31(+) recent thymic emigrant T(reg) cell (RTE-T(reg)) frequency (p<0.01), and T-cell receptor excision circle levels in T(reg) cells (p<0.01) were lower in CHF patients than in non-CHF controls. Combined annexin-V and 7-AAD staining showed that peripheral T(reg) 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 T(reg)-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.Our data suggested that the T(reg)-cell defects of CHF patients were likely caused by decreased thymic output of nascent T(reg) cells and increased susceptibility to apoptosis in the periphery. |
url |
http://europepmc.org/articles/PMC3174174?pdf=render |
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