Systems vaccinology of the BNT162b2 mRNA vaccine in humans P ra bh u S. A ru na ch al am , M ad el ei ne K. D.

BackgroundIschemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling.Methods and ResultsThe number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling.ConclusionTreg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling.

Background— Lymphocytes play an important role in the progression of atherosclerosis. Recently, hypoxia inducible factor-1 (HIF-1) was found to attenuate inflammation by regulating T cell activation and cytokine production. We studied the effects of overexpression of HIF-1α in ApoE knockout murine lymphocytes, on experimental atherosclerosis. Methods and Results— ApoE −/− mice were submitted to intravenous hydrodynamic injection of empty plasmid or HIF-1αP564A (HIF-1α mutated stabilized construct). Robust expression of HIF-1α was evident in spleen cells of recipient animals. Increased expression of IL-10 as well as decreased expression of IFN-γ was measured in splenocytes of HIF-1α–treated mice by RT-PCR. One week postinjection, antibody array analysis revealed a pattern consistent with a T helper 1 to T helper 2 shift. On sacrifice, assessment of aortic sinus lesions revealed a significant reduction in plaque size in HIF-1α injected mice. A reduced expression of IFN-γ was evident in CD4+ spleen-derived lymphocytes and aortas of HIF-1α–injected mice. Conclusions— HIF-1α expression in mouse lymphocytes is associated with a reduced IFN-γ expression and attenuation of experimental atherosclerosis.