Abstract 174: T Cells Promote the Progression of Hypertension and Renal Injury during Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent hypertension and is a novel disease model to study the link between immune system activation and the development of hypertension. T cells have a central role in the pathogenesis of autoimmune disorders and were recently reported to promote angiotensin II and salt-sensitive hypertension. Despite their well known role in the pathogenesis of autoimmune disease and recent data suggesting an important role in the pathogenesis of hypertension, whether T cells mechanistically contribute to the prevalent hypertension during SLE remains unclear. In order to test this, experiments were designed to determine whether inhibition of T cell proliferation attenuates the progression of hypertension and renal injury in female SLE mice with established renal injury (albuminuria ≥ 100 mg/dL). SLE and control mice were administered either antibody to CD3, a component of the T cell receptor expressed on all T cells, or an anti-IgG isotype control for up to 4 weeks (intranasally; 25 μg/week). Splenic CD3 + CD4 + T cells were increased in SLE mice compared to controls (7.0 ± 4.2% vs. 3.1 ± 1.5% gated) and were reduced after the anti-CD3 treatment (2.4 ± 1.1% gated), likely reflecting a reduction in spleen weight. Anti-dsDNA autoantibodies characteristic to SLE were increased in vehicle-treated SLE mice compared to controls (19.8 ± 7.3 vs. 0.74 ± 0.07, n=10) and were blunted in the anti-CD3 treated SLE mice (9.7± 3.8, n=10). Blood pressure (mmHg) was increased in SLE mice compared to controls (156 ± 3 vs. 112 ± 4, p=0.001), and was lower in anti-CD3 treated SLE mice (137 ± 4; p=0.01) but not controls (117 ± 2). In anti-IgG treated SLE mice, albuminuria increased (+38.9 ± 36.8%) over the course of the study, whereas albuminuria in anti-CD3 treated SLE mice was unchanged (-2.53 ± 17.3%). Preliminary renal histology suggests that the anti-CD3 treatment attenuated the progression of glomerulosclerosis and preserved renal vascular structure (i.e., interlobular arteries, vasa recta). No renal injury was observed in the control mice. These data suggest that T cells have an important mechanistic role in the progression of autoimmune-associated hypertension, perhaps by promoting renal vascular structural changes and injury.