CD73 Rather Than CD39 Is Mainly Involved in Controlling Purinergic Signaling in Calcified Aortic Valve Disease

Abstract

The study aimed to compare composition of peripheral blood T-cell subsets and assess their surface expression of CD39 and CD73 ectonucleotidases in patients with severe and moderate aortic stenosis (AS) as well as to evaluate involvement of T-cell-mediated immune processes in valve calcification. The study was performed with 38 patients suffering from severe calcified aortic stenosis (SAS), 33 patients with MAS, and 30 apparently healthy volunteers (HVs). The relative distribution and percentage of T-cell subsets expressing CD39 and CD73 were evaluated by flow cytometry. T helper (Th) and cytotoxic T-cell subsets (Tcyt) were identified by using CD3, CD4, and CD8 antibodies. Regulatory T cells (Tregs) were characterized by the expression of CD3, CD4, and high IL-2R alpha chain (CD25high) levels. CD45R0 and CD62L were used to assess differentiation stage of Th, Tcyt, and Treg subsets. It was found that MAS and SAS patients differed in terms of relative distribution of Tcyt and absolute number of Treg. Moreover, the absolute number of Tcyt and terminally differentiated CD45RA-positive effector T-cells (TEMRA) subset was significantly higher in SAS vs. MAS patients and HVs. However, the absolute and relative number of naïve Th and the absolute number of Treg were significantly higher in MAS vs. SAS patients; the relative number of naïve Tregs was significantly ( p < 0.01) decreased in SAS patients. It was shown that CD73 expression was significantly higher in SAS vs. MAS patients noted in all EM, CM, TEMRA, and naïve Th cell subsets. However, only the latter were significantly increased ( p = 0.003) in patients compared with HVs. SAS vs. MAS patients were noted to have significantly higher percentage of CD73+ EM Tcyt ( p = 0.006) and CD73+ CM Tcyt ( p = 0.002). The expression of CD73 in patients significantly differed in all three Treg populations such as EM ( p = 0.049), CM ( p = 0.044), and naïve ( p < 0.001). No significant differences in CD39 expression level was found in MAS and SAS patients compared with the HV group. Overall, the data obtained demonstrated that purinergic signaling was involved in the pathogenesis of aortic stenosis and calcification potentially acting via various cell types, wherein among enzymes, degrading extracellular ATP CD73 rather than CD39 played a prominent role.

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

“…CM T cells are less-differentiated, long-lived memory cells, with very limited effector functions. They recirculate through secondary lymphoid organs and demonstrate high proliferative and renewal capacity [ 13 , 14 , 34 , 35 ]. Central memory T cells produce high amounts of IL-2 and low levels of other effector cytokines (IL-4, IL-5, and IFN-γ).…”

“…The gating strategy for the main T-cell subsets was described previously [ 11 ] and is shown in Figure 1 . This method was developed by Sallusto et al [ 12 ] and was validated by our group [ 13 , 14 ]. The hierarchical tree histogram in Figure 2 was gated on the CM Th and EM Th subsets as an example.…”

Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19

“…Optimal combinations of the antibodies conjugated with various fluorochromes were used according to a previously published method. This method was developed by Sallusto et al [ 47 ] and validated by our group [ 48 , 49 ].…”

Overview of multifunctional Tregs in cardiovascular disease: From insights into cellular functions to clinical implications

“…However, evidence for Tregs cell function can be drawn from their involvement in atherosclerosis. 39,45,152 Furthermore, IL-10, secreted by Tregs, contributes to a dormant microenvironment by inhibiting monocyte and macrophage inflammation and cytokine production, thereby reducing their ability to adhere to the valve endothelial wall and infiltrate the leaflet. Circulating IL-10 has been shown to correlate negatively with aortic valve calcium formation.…”