T cell activation and their infiltration into the vascular wall in Angiotensin II dependent hypertension.

Hypertension is a major source of morbidity and mortality. The mechanisms linking it to inflammation and atherosclerosis are poorly understood. We have investigated the effects of angiotensin II infusion (500 ng/kg/min) on T cell activation and its role in hypertension and vascular dysfunction. Ang II infusion increased number of activated CD4+ cells with CD69+ (6.0±1.3% vs 9.9±1.5%;p<0.01;n=10) and CD25+ (7.6±0.5% vs 11.1±1.5%;p<0.01) in blood. Ang II also increased T cell CD44 and CCR5 in T cells and RANTES chemokine mRNA in aorta. These were accompanied by increased T cell infiltration into the aortic adventitia and periadventitial fat (immunohistochemistry for CD3 and TcR) and quantitative real time PCR (>50 fold increase of CD3 mRNA). Flow cytometry of aortic cell suspensions, showed a particular increase in numbers of CD4+ T cells and CD3+CD4−CD8− double negative (DN) T cells (30% of aortic T cells). Aortic T cells preferentially expressed CCR5 on their surface (67±4%vs5±1% in blood). DN T cells expressing á/â T cell receptors, increased from 35±2 to 51±9%. T cell responses to Ang II are potentially important in the pathogenesis of hypertension and vascular dysfunction, as the hypertension caused by Ang II was reduced in RAG-1−/− mice (lacking T and B cells), compared to WT (telemetry 124±4 vs. 142±4 n=12 p<0.01). The alteration of endothelial function caused by Ang II was virtually absent in RAG-1−/− mice as was the Ang II - induced aortic wall hypertrophy. Adoptive transfer of T cells, but not B cells restored these hypertensive responses to Ang II. We hypothesize that Ang II activates T cells, which infiltrate the vessels and can stimulate vascular dysfunction and hypertension.