Abstract 043: Dendritic Cells Mediate Renal T Cell Activation in Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 68; no. suppl_1
• Main Authors: Rudemiller, Nathan P, Zhang, Jiandong, Hammer, Gianna E, Yu, Yen-Rei A, Griffiths, Robert, Gunn, Michael D, Crowley, Steven D
• Format: Journal Article
• Language: English
• Published: 01.09.2016
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.68.suppl_1.043

Abstract only Activated T lymphocytes exacerbate hypertension in part by infiltrating the kidney to promote sodium retention. Dendritic cells (DCs) are the most potent antigen presenting cells that activate T cells and have been shown to contribute to hypertension. The current studies therefore explored whether DC-mediated activation of renal T cells can exaggerate the chronic hypertensive response to angiotensin (Ang) II. First, we confirmed that renal T cells undergo DC-mediated activation during the initiation of hypertension by analyzing immune cell populations in renal tissue via flow cytometry. In Fms-like tyrosine kinase 3 ligand-deficient (FLT3L KO) mice that lack DCs, the proportions of effector (CD44 hi CD62 lo ) T cells in the kidney were similar to wild-type (WT) controls at baseline (50±3 vs. 52±7% of CD3 + cells). However, after 5 days of Ang II-induced hypertension, the proportions of effector T cells were dramatically higher in the WT kidney versus the FLT3L KOs (69±3 vs. 52±3% of CD3 + cells; p<0.01), indicating that DCs activate T cells in hypertension. As DCs activate T cells in local lymph nodes, we phenotyped T cell subsets in the kidney lymph node (KLN) following 4 weeks of hypertension and detected elevated proportions of effector CD4 + T cells compared to baseline (10.7±2.0 vs. 6.9±0.8% of CD4 + T cells). The ubiquitin-editing protein A20 in DCs suppresses their capacity to stimulate T cells. Thus, mice with heterozygous deletion of A20 in DCs (CD11c-cre A20 flox/wt = DC ACT) harbor spontaneously active DCs that enhance T cell activation. To test the contribution of DC-mediated T cell activation to hypertension, we measured blood pressures in WT and DC ACT mice during 4 weeks of chronic Ang II infusion (300ng/kg/min). While MAPs were similar in the 2 groups at baseline, the DC ACT mice had an exaggerated chronic hypertensive response (143±2 vs. 131±4 mmHg; p=0.04) with more severe cardiac hypertrophy (7.3±0.3 vs. 6.4±0.4 mg/gm body wt; p<0.04). The KLNs from the DC ACT animals also contained higher proportions of effector T cells than controls (12.1±0.2 vs. 8.2±0.5% of CD3 + cells; p<0.01). In conclusion, DC-mediated activation of T cells promotes blood pressure elevation by facilitating the accumulation of effector T cells in the kidney during hypertension.