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

doi:10.1016/j.jacbts.2022.05.005

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

JACC Basic Transl Sci. 2022 Jul 6;7(10):1038-1049. doi: 10.1016/j.jacbts.2022.05.005. eCollection 2022 Oct.

Authors

Vinay Kumar^{1

2}, Rachel Rosenzweig^{1

2}, Suman Asalla^{1

2}, Sarita Nehra^{1

2}, Sumanth D Prabhu³, Shyam S Bansal^{1

2

4}

Affiliations

¹ Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
² The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
³ Division of Cardiology, Department of Medicine, Washington University, St Louis, Missouri, USA.
⁴ Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

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.

Keywords: AT, adoptive transfer; HF, heart failure; IL, interleukin; LV, left ventricular; MFI, mean fluorescence intensity; MI, myocardial infarction; PBS, phosphate-buffered saline; T lymphocytes; TCR, T-cell receptor; TNF, tumor necrosis factor; TNFR1, tumor necrosis factor receptor 1; Tcm, memory T cell; WT, wild type; heart failure; left ventricular remodeling; mLN, mediastinal lymph node; myocardial infarction; tumor necrosis factor receptors.

Abstract

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