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Background Macrophage infiltration and activation in myocardium are hallmarks of acute cardiac inflammatory response to high blood pressure.However, the underlying mechanisms remain elusive.Aim In this study, we aimed to explore the role of CD8+ T cells in hypertension induced acute inflammatory response and find the molecular mechanism of CD8+ T in cardiac recruitment and activation of macrophages.Methods Angiotensin Ⅱ (1500ng/kg.min) infusion was used to build the model of hypertension induced acute cardiac inflammatory response.The pathology, molecular biology and flow cytometry analysis methods were used to detect collagen deposition, inflammatory cell infiltration and expression of inflammatory cytokines in hypertensive hearts.The co-culture of CD8+ T cells and macrophages in vitro was used to analyze the effect of CD8+ T on the activation and recruitment of macrophages.Results We found that: 1) there was a large number of CD8+ T cells infiltrated in hypertensive mice heart after Ang Ⅱ infusion.2) Mice with CD8 gene-targeted (CD8 knockout) or CD8+ T cells depleted by Ab showed significantly reduced cardiac inflammatory response and cardiac fibrosis formation to the elevation of blood pressure after angiotensin Ⅱ (Ang Ⅱ) infusion, compared with wild type mice; whereas CD8 knockout mice reconstituted with CD8+ T cells restored the sensitivity to Ang Ⅱ.3) More importantly, CD8+ T ceils were required for macrophage infiltration in myocardium and subsequent activation to express proinflammatory cytokines and chemokines.4) Furthermore, macrophage activation required direct contact with activated CD8+ T cells, but with TCR dispensable.TCR-independent activation of macrophages was further confirmed in MHC class Ⅰ-restricted OVA-specific TCR transgenic mice, which showed a CD8+ T cell activation and cardiac proinflammatory response to Ang Ⅱ similar to that of wild-type mice.5) Only myoeardium-infiltrated, but not peripheral, CD8+ T cells were specifically activated by Ang Ⅱ, possibly by the cardiac IFN-γ that drove IFN-γR+ CD8+ T cell infiltration and activation.Conclusion Thus, this work identified a TCR-MHC Ⅰ independent innate nature of CD8+ T cells that was critical in initiating and augmenting immune response to acute elevation of blood pressure.These findings would provide a novel potent target for the protection of hypertension induced cardiac damage.