γδ T Cells Mediate Pressure Overload-Induced Cardiac Inflammation, Hypertrophy, Heart Failure Development, and Heart Failure Progression

Abstract

Gamma delta T cells (γδ T cells) are T cells that have a γδ T-cell receptor (TCR) on their surface. γδ T cells display broad functional plasticity following recognition of infected or injured cells by production of cytokines and chemokines, and cytolysis of the infected or injured cells. However, the role of γδ T cells in heart failure (HF) development and HF progression is unknown. To investigate the role of γδ T cells in HF development and progression, we studied the effect of transverse aortic constriction (TAC) on cardiac inflammation, hypertrophy, and dysfunction in both wild type and TCRδ gene deficient (TCRδ−/−) mice, as TCRδ−/− mice have no γδ T cells. Interestingly, TCRδ−/− significantly attenuated TAC-induced left ventricular (LV) hypertrophy as evidenced by less increase of LV weight and its ratio to bodyweight or tibial length. TCRδ−/− also significantly attenuated TAC-induced increase of lung weight, right ventricular weight, and their ratio to bodyweight or tibial length. TCRδ−/− also significantly reduced TAC-induced decease of LV ejection fraction and LV fractional shortening, and LV dilatation. Furthermore, TCRδ−/− significantly attenuated TAC-induced LV cardiomyocyte hypertrophy, fibrosis, and immune cell infiltration. Moreover, we found that TCRδ−/− significantly reduced TAC-induced infiltration and activation of pulmonary antigen presenting cells, CD4 T cells and CD8 T cells. Together, these data indicate that γδ T cells exert an important role in promoting systolic overload-induced cardiac inflammation, HF development, and HF progression. This work was supported by NIH research grants R01HL161085, R01HL139797, P20GM104357, and P30GM149404. 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.