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

Chronic left ventricular (LV) failure or heart failure (HF) often progress to pulmonary remodeling and right ventricular (RV) hypertrophy even with optimal medical care. Cytotoxic CD8 + T cells play an important role in modulating virus infection and tissue injury by producing proinflammatory cytokines and cytolysis of the infected or injured cells. However, the role of CD8 + T cells in heart failure (HF)-induced lung remodeling and RV hypertrophy is unknown. To determine the role of CD8 T cells in modulating HF progression under preexisting HF conditions, wild type mice with existing LV failure produced by transverse aortic constriction (TAC) were randomized to depletion of cytotoxic CD8 + T cells, regulatory T cells (Tregs), or both by using specific blocking antibodies. The cardiac function, lung inflammation, fibrosis, vascular remodeling, and right ventricular remodeling were determined. As anticipated, LV failure caused lung inflammation and activation of pulmonary CD4 + T cells and CD8 + T cells. Interestingly, 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. LV failure was associated with an increased ratio of activated T cells to Tregs, and Treg depletion exacerbated lung inflammation and the progression of LV failure. Treg depletion also exacerbated the lung CD4 + and CD8 + T cell infiltration, and the percentage of effector memory T cells (Tem) in HF mice. Depletion of CD8 + T cells was suffcient to rescued HF mice from the exacerbated lung inflammation and the progression of LV failure that was caused by Treg depletion. These findings demonstrate that CD8 + T cells play a critical role in promoting the transition from LV failure to lung remodeling and RV hypertrophy. NIH funding. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.