Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Abstract

Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2-34.9) vs. 12.6% (IQR 8.3-27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar Cells 2020, 9, 295 2 of 19 size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates.

The Regulatory Role of T Cell Responses in Cardiac Remodeling Following Myocardial Infarction

“…However, OMT cannot promote a regenerative effect in the ischemic area. To date, target therapies are improving and include specific antibodies and the exogenous ubiquitin helping in reducing the scar area in rodent models after cardiac injury [13,14]. In addition, stem cell-based therapies had developed with improvement in cardiac function, however, the overall beneficial effects are relatively modest with fundamental mechanisms of stem cell-mediated repair being largely unknown.…”

Emerging Roles for Dendritic Cells in Heart Failure

“…These observations are associated with increased T cell infiltration of the myocardium. Multiple studies have demonstrated that neutralization of T cell activation appears to protect against myocardial fibrosis and ventricular dysfunction [43,44]. Anti-CD3 antibody treatment in a rat model of myocardial infarction reduced scar formation [44].…”

SERS Resolving of the Significance of Acetate on the Enhanced Catalytic Activity of Nanozymes

“…2021-KYLY-020010) was approved by the Institutional Review Board of China–Japan Union Hospital of Jilin University and was performed following the guidelines and regulations established by the China–Japan Union Hospital of Jilin University to protect human subjects. Exosomes were isolated from cancer cell serum by hypervelocity centrifugation as reported previously in the literature. − Each bottle of 500 μL patient serum supernatant was thawed at 4 °C and then placed into a centrifuge tube equipped with a 32Ti rotor. The last two digits were strictly balanced, centrifuged at 500 g speed for 15 min at 4 °C, and removed the precipitate.…”