Abstract 085: The Role of CD70 in Vascular Function

Abstract

We have recently shown that CD70 is important in formation of effector memory T cells and that these cells seem to enhance the hypertensive response and end organ damage caused by repeated hypertensive stimuli. CD70 has traditionally been identified on antigen presenting cells and is thought to interact with CD27 on T cells, promoting proliferation and memory cell formation. The precise cell types that express CD70 and the role of CD70 on non-immune cells has not previously been investigated. In our prior study, we showed that hypertension is associated with a marked increase in CD70 surface expression on dendritic cells (DCs) and macrophages. To examine the specific effect of DC CD70, we performed adoptive transfer of DCs from hypertensive WT mice to normotensive CD70 -/- mice and from hypertensive CD70 -/- mice to normotensive WT mice. The recipient mice were treated with a normally subpressor dose of ang II (140 ng/kg/min). Interestingly the CD70 -/- recipients were protected from the development of hypertension, despite receiving WT DCs from hypertensive donors. In contrast, the WT recipeints that received CD70 -/- DCs developed modest hypertension, indicating that non-DC sources of CD70 likely contribute to the hypertensive phenotype. Studies of mesenteric vascular reactivity showed that CD70 -/- mice have markedly impaired endothelium-dependent vasodilatation to acetylcholine compared to WT mice (43±10 vs 25 ± 3 %) at baseline. In contrast, there were no differences in relaxation responses to sodium nitroprusside. In additional experiments, we showed that human umbillical vein endothelial cells express CD70 mRNA and that this is increased by > 30 fold by laminar shear stress (15 dynes/cm2) compared to oscillatory shear. Finally, using immunohistochemistry, we identified CD70 protein localized to resistance vessels of the kidney of ang II-treated mice. These data identify a new role of CD70 in modulating vascular function independent of its role on antigen presenting cells in memory T cell formation.