TNFR1 Contributes to Activation-Induced Cell Death of Pathological CD4+ T Lymphocytes During Ischemic Heart Failure

Vinay Kumar, Rachel Rosenzweig, Suman Asalla, Sarita Nehra, Sumanth D. Prabhu, Shyam S. Bansal

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

CD4+ T cells turn pathological during heart failure (HF). We show that the expression of tumor necrosis factor (TNF)-α and tumor necrosis factor receptor (TNFR1) increases in HF-activated CD4+ T cells. However, the role of the TNF-α/TNFR1 axis in T-cell activation/proliferation is unknown. We show that TNFR1 neutralization during T-cell activation (ex vivo) or the loss of TNFR1 in adoptively transferred HF-activated CD4+ T cells (in vivo) augments their prosurvival and proliferative signaling. Importantly, TNFR1 neutralization does not affect CD69 expression or the pathological activity of HF-activated TNFR1−/− CD4+ T cells. These results show that during HF TNFR1 plays an important role in quelling prosurvival and proliferative signals in CD4+ T cells without altering their pathological activity.

Original languageEnglish
Pages (from-to)1038-1049
Number of pages12
JournalJACC: Basic to Translational Science
Volume7
Issue number10
DOIs
StatePublished - Oct 2022

Keywords

  • T lymphocytes
  • heart failure
  • left ventricular remodeling
  • myocardial infarction
  • tumor necrosis factor receptors

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