CD8 T cells exert a critical role in the transition from left heart failure to lung remodeling and right ventricular hypertrophy

Abstract

BackgroundPatients with left ventricular (LV) failure or heart failure (HF) often progress to right ventricular (RV) hypertrophy and/or failure even with optimal medical care. Previously, we have shown a potential role for regulatory T cells (Tregs) in suppressing LV failure progression. However, the particular leukocyte subset(s) that promote the transition from LV failure to RV hypertrophy and failure are unknown. Here, we investigated the role of cytotoxic CD8+T cells in this progression.MethodsMice with LV failure produced by transverse aortic constriction (TAC) were randomized to depletion of cytotoxic CD8+T cells using specific blocking antibodies. The cardiac function, lung inflammation, fibrosis, vascular remodeling, and right ventricular remodeling were determined.ResultsLV failure caused lung inflammation and lung T cell activation involving both CD4+and CD8+T cell activation. Depletion of CD8+ T cells dramatically attenuated the increase of lung weight, lung inflammation, lung vascular remodeling, and RV hypertrophy in mice with existing LV failure.ConclusionsOur findings demonstrate that CD8+T cells play a critical role in promoting the transition from LV failure to lung remodeling and RV hypertrophy, indicating that modulation of CD8+T cell activity may represent a new approach to heart failure therapy.Support or Funding InformationThis study was supported by research grants 81470512 and 81570355 from Nature Science Foundation, and Grants HL098669, HL102597, R01HL105406 from the National Institutes of Health, and a grant in aid from American Heart Association.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.