Background
Autoantibodies against the second extracellular loop of the β(1)-adrenergic receptor (β(1)-AA) not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the β(1)-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β(1)-AA isolated from the sera of dilated cardiomyopathy (DCM) patients caused the proliferation of T cells and the secretion of cytokines.
Conclusions
These results demonstrate that β(1)-AA isolated from DCM patients binds to β(1)-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β(1)-AR/cAMP/PKA and p38 MAPK pathways.
Methods
Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and β(1)-AA was detected using ELISA. The CD3(+)T lymphocytes were selected separately through flow cytometry and the effect of β(1)-AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK.
Results
β(1)-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β(1)-adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of β(1)-AA. β(1)-AA also inhibited the secretion of interferon-γ (IFN-γ) while promoting an increase in interleukin-4 (IL-4) levels. Conclusions: These results demonstrate that β(1)-AA isolated from DCM patients binds to β(1)-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β(1)-AR/cAMP/PKA and p38 MAPK pathways.