CD8+ T cells contribute to arterial aging in mice.

We have previously reported that T cells accumulate in the arteries of old mice and mechanistically contribute to the development of age-related arterial dysfunction. However, the specific T cell subtype that is the primary contributor to arterial aging is unknown. There is substantial evidence that CD8+ T cells are more susceptible to the effects of aging compared with their CD4+ counterparts. We hypothesized that CD8+ T cell-specific depletion would ameliorate large-artery stiffness and augment endothelium-dependent dilation in old mice but not in young mice. We observed that old mice exhibited a greater accumulation of CD8+, but not CD4+, T cells in the aorta and mesentery compared with their young counterparts. Further, pharmacological depletion of CD8+, but not CD4+, T cells resulted in lower aortic stiffness and blunted aortic collagen. In addition, old CD8+, but not CD4+, depleted mice demonstrated augmented endothelium-dependent dilation via greater nitric oxide bioavailability. These data indicate that CD8+ T cells are the specific T cell subtype that contributes to age-related arterial dysfunction.