PLoS ONE (Jan 2011)

Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0024272
Journal volume & issue
Vol. 6, no. 9
p. e24272

Abstract

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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.