Pro-remodeling effect of autoantibody against β₁-adrenoceptor on cardiomyocytes involves T cells dysfunction under...

Autoantibody against β₁-adrenoceptor (β₁-AA) has been shown to be closely linked to the aggravation of heart failure. Removal of β₁-AA remarkably attenuated patients' cardiac dysfunction. We found that β₁-AA induced rat heart failure with increased CD4⁺ T cells. However, whether or not β₁-AA interacts with T cells isolated from heart failure patients remains unknown. Twenty-one β₁-AA-negative heart failure patients were divided into those taking β-adrenergic blocker and those not. The effects of β₁-AA monoclonal antibodies (β₁-AAmAb) on T cells proliferation were detected using the CCK-8 assay. IFN-γ and IL-4 production by human T cells were measured by after the administration of β₁-AAmAb. The levels of cardiomyocyte apoptosis and hypertrophy were detected after co-cultured with the supernatant of T cells pre-stimulated by β₁-AAmAb. It was found that β₁-AAmAb promoted T cell proliferation via the β₁-AR/cAMP/PKA pathway in patients who not take β-blocker. β₁-AAmAb inhibited the characteristic cytokine secretion of Th1, IFN-γ, but had no significant effect on the Th2 cytokine IL-4. Supernatant resulted from the T cells pre-treated with β₁-AAmAb induced cardiomyocytes remodeling, as evidenced by increased levels of cardiomyocytes apoptosis and hypertrophy. We propose that heart failure is likely to be an interference factor for Th-mediated immunity, and the presence of β₁-AAmAb may aggravate this effect and deteriorate concomitant inflammatory injury in cardiomyocytes, partially via β₁-AR/cAMP/PKA pathway.