Perturbed T cell IL-7 receptor signaling in chronic Chagas disease

J Immunol. 2015 Apr 15;194(8):3883-9. doi: 10.4049/jimmunol.1402202. Epub 2015 Mar 13.


We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections with signs of T cell exhaustion. Alterations in cytokine receptor signal transduction have emerged as one of the cell-intrinsic mechanisms of T cell exhaustion. In this study, we performed an analysis of the expression of IL-7R components (CD127 and CD132) on CD4(+) and CD8(+) T cells and evaluated IL-7-dependent signaling events in patients at different clinical stages of chronic chagasic heart disease. Subjects with no signs of cardiac disease showed a decrease in CD127(+)CD132(+) cells and a reciprocal gain of CD127(-)CD132(+) in CD8(+) and CD4(+) T cells compared with either patients exhibiting heart enlargement or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of CD127 and the upregulation of CD132 on T cells. IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were lower in T. cruzi-infected subjects compared with uninfected controls. The serum levels of IL-7 were also increased in chronic chagasic patients. The present study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a potential mechanism of T cell exhaustion in chronic T. cruzi infection.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Chagas Disease / immunology*
  • Chagas Disease / pathology
  • Chronic Disease
  • Female
  • Humans
  • Interleukin Receptor Common gamma Subunit / immunology
  • Interleukin-7 / immunology
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Receptors, Interleukin-7 / immunology*
  • STAT5 Transcription Factor / immunology
  • Signal Transduction / immunology*
  • Trypanosoma cruzi / immunology*


  • BCL2 protein, human
  • IL2RG protein, human
  • IL7 protein, human
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-7
  • STAT5 Transcription Factor