CD4+ T cells do not contribute to age-related arterial dysfunction in mice 3630

Abstract Description Previously we have demonstrated that T cells accumulate in the arteries of old (22-24mo) animals. We have also demonstrated that pharmacological depletion of pan (CD3+) and cytotoxic (CD8+) T cells results in improved large artery stiffness and greater endothelial dependent vasodilation via greater nitric oxide bioavailability. To determine the contributions, if any, that helper (CD4+) T cells have in age-related arterial dysfunction, we pharmacologically depleted CD4+ T cells in mice. Young (4-6mo) and old (22-24mo) male C57bl/6 mice were injected with either anti-CD4 or control antibodies every 5 days for 28 days. T cells in the aorta and mesenteric adipose tissue were quantified using flow cytometry. Aortic stiffness was determined using pulse-wave velocity and endothelial dependent dilation was determined using pressure myography. We found an age-associated accumulation of CD8+, but not CD4+ T cells both the aorta and mesentery. Also, CD4+ T cells were absent in mice who received the anti-CD4 antibodies. Old anti-CD4 treated mice did not exhibit any improvements in either aortic stiffness nor greater endothelial dependent vasodilation compared to old CD4+ intact mice. Young mice regardless of CD4+ T cell status did not exhibit differences in arterial function. Our results demonstrate that CD4+ T cells do not contribute to age-related arterial dysfunction and confirm our findings that CD8+ T cells may be the primary drivers of age-related arterial dysfunction. Funding Sources Funding: NIH K01AG061271 (Trott), 1R01AG086447-01, R01AG060395 (Donato, Co-I Trott); AHA: AHA940023 (Trott) Topic Categories Immune Mechanisms of Human Disease (HUM)