Circulating Senescent Angiogenic T Cells Are Linked With Endothelial Dysfunction And Systemic Inflammation In Hypertension

Objective: Angiogenic T cells (T-ang cells), a recently discovered T-cell subset, have been reported involved in the repair of endothelial injury. The purpose of this study was to explore the correlation of immunologic senescence and pro-inflammatory capacity of T-ang cells with endothelial dysfunction in hypertensive patients. Methods: Immunological characteristics of T-ang cells (CD3(+)CD31(+)CXCR4(+)) from hypertensive patients with or without endothelial dysfunction were elucidated by surface immunophenotyping and intracellular cytokine staining. Endothelial function was measured by flow-mediated dilation (FMD). Results: The frequency of CD28(null) subset in CD4(+) T-ang cells was notably elevated in hypertensive patients with endothelial dysfunction, which was negatively associated with FMD. The high frequency of CD28(null)CD4(+) T-ang cells was an independent risk factor of endothelial dysfunction with good diagnostic performance in ROC curve analysis. Immunophenotyping revealed that this specific subset of T-ang cells exhibited senescent profile and has low hTERT expression. CD28(null)CD4(+) T-ang cells produced high levels of inflammatory cytokines, IL-6, IFN-gamma and TNF-alpha, and significantly correlated with the systemic inflammation in hypertensive patients with endothelial dysfunction. Conclusion: Collectively, our findings demonstrate for the first time that CD28(null) subset in CD4(+) T-ang cells with senescent and pro-inflammatory phenotype is dependently correlated with impaired FMD and systemic inflammation, which might contribute to the immunopathologic mechanism of endothelial dysfunction. Identification of a pathogenic CD4(+) T-ang-cell subset lacking CD28 may offer opportunities for the evaluation and management of endothelial dysfunction in hypertension.