BackgroundNumerous studies have reported significantly elevated titers of serum autoantibody against the second extracellular loop of (1)-adrenoceptor ((1)-AA), a catecholamine-like substance with (1)-adrenergic activity, in patients with heart failure. Although evidence demonstrates that this autoantibody may alter T cell proliferation and secretion, the role of T lymphocytes in heart failure induced by (1)-AA remains unclear. The current study was designed to determine whether T cell disorder contributes to heart failure induced by (1)-AA.Methods and Results(1)-AA monoclonal antibodies ((1)-AAmAb) produced using the hybridoma technique were administered in wild-type mice or T lymphocyte deficiency nudes for 12weeks. T lymphocytes from heart failure patients and neonatal cardiomyocytes were utilized in vitro. Mouse protein antibody array analysis was employed to detect the cytokines responsible for (1)-AAmAb-induced heart failure. Compared to wild-type mice, T lymphocyte deficiency mice prevented cardiac function from getting worse, attenuated adverse remodeling, and ameliorated cardiomyocyte apoptosis and fibrosis. As shown by protein array, the serum level of interleukin (IL)-6 was significantly lower in the nude group as compared to wild-type after (1)-AAmAb treatment. Mechanistic studies in vitro demonstrated that T lymphocyte culture supernatants stimulated by (1)-AAmAb caused direct damage in the cardiomyocytes, and (1)-AAmAb promoted proliferation of T lymphocytes isolated from patients with heart failure and increased IL-6 release. IL-6-specific siRNA virtually abolished cardiomyocyte apoptosis, suggesting that IL-6 may be a key cytokine released by T lymphocytes and responsible for (1)-AAmAb-induced cardiac remodeling.ConclusionsCollectively, we demonstrate that (1)-AAmAb-induced cardiac remodeling via mediating T lymphocyte disorder and releasing a variety of IL-6.