Abstract 15314: Autoantibody Against β1-Adrenoceptor Facilitates the Activation of Regulatory T Cells (Tregs), but Attenuates the Tregs’ Cardioprotective Effects in the Presence of High Concentration
Introduction: Numerous studies indicate that the existence of autoantibodies and CD4+T cells dysfunction constitute the main immunological mechanism in heart failure. Autoantibody against β1-adrenoceptor (β1-AA) is frequently detected in the sera of heart failure patients. Removal of β1-AA attenuates cardiac dysfunction and leads to an increase in the number of regulatory T cells (Tregs). Defective Tregs has been found in patients with heart failure which is also related to autoantibody generation. β1-AA induces histopathological damage on murine hearts with over-activated CD4+T cells, and promotes T cells proliferation. However, whether β1-AA interfere with Tregs is unknown.
Hypothesis: We assume that β1-AA damages Tregs and therefore deteriorates myocardial cells injury.
Methods: 1) Healthy BALB/c and Nude mice were subjected to intraperitoneal injection with β1-AR monoclonal antibody, and serum were collected to detect the level of β1AA and Tregs related cytokines. Doppler echocardiography was performed to detect the changes on heart function. 2) The CD4+CD25+Tregs were selected through murine spleen mononuclear cells and the effect of β1-AA on Tregs differentiation was examined by flow cytometry. The activation of Tregs was reflected by IL-10 level. Effector T cells proliferation assay was measured by CFSE staining. Apoptosis of cardiomyocytes was evaluated using Annexin-V and propidium iodide staining.
Results: 1) β1-AA promoted the expression of cytokines related to Tregs differentiation (IL-2/IL-2 R, TGF-β), immigration (CCR6, CXCR3) and suppressive function (IL-10/IL-10 R, CTLA-4, Granzyme B). 2) β1-AA facilitated the Tregs differentiation partially through β1-AR pathways in vitro (n=6). 3) Tregs function was regulated by different concentrations of β1-AA (β1-AA suppressed IL-10 secretion at a concentration of 10-6 and 10-7 mol/l. However, 10-8 mol/l β1-AA had a opposite effect) and attenuated the Tregs’ cardioprotective effects at high concentrations (n=6).
Conclusions: It is suggested that β1-AA facilitates the activation of Tregs partially via receptor pathway, but has bidirectional impacts on Tregs function which attenuates the Tregs’ cardioprotective effects in the presence of high concentration.
Author Disclosures: W. Xu: None. Y. Du: None. Y. Bai: None. Y. Dong: None. W. Wang: None. H. Liu: None.
- © 2016 by American Heart Association, Inc.