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-γ and TNF-α, 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.