T Cell Engraftment, survival, and the effect on large artery stiffness

Low-grade inflammation is persistent with advancing age in healthy people and mice. Endothelial cells and large arteries increasingly express pro-inflammatory cytokines, coinciding with increased T cell infiltration into the aorta. Arterial stiffness is an independent risk factor for cardiovascular diseases, and stiffness increases with age. T cells particularly affect vascular dysfunction, and we have shown that T cell depletion in old mice prevented elevations in stiffness. We sought to understand how the aged phenotype of T cells affects arterial stiffness and arterial T cell infiltration. T cells were isolated from young or old C57BL/6 mice and adoptively transferred into young or old RAG1-/- mice, which lack T or B cells. After 5 weeks, arterial stiffness was measured via pulse wave velocity (PWV). T cells in the circulation, but not the aorta, were higher in young mice, suggesting a better environment for T cells to survive or proliferate compared to old mice. CD4:CD8 ratio was inverted in the aorta and circulation, with a lower ratio in young mice. CD4+ T cell percent was higher in old mice, with young CD4+ cells better able to survive or proliferate in the aorta. T cell functional state (naïve, effector memory, or central memory) was highly dependent on T cell age, with similar patterns between CD4+ and CD8+ T cells. This did not translate to varied arterial stiffness with young or old T cells; mouse age drove elevated PWV in old mice. These findings highlight that vascular, not T cell changes associated with aging drive age-related arterial dysfunction.