Sex Differences in T-Lymphocyte Tissue Infiltration and Development of Angiotensin II Hypertension

Abstract

There is extensive evidence that activation of the immune system is both necessary and required for the development of angiotensin II (Ang II)–induced hypertension in males. The purpose of this study was to determine whether sex differences exist in the ability of the adaptive immune system to induce Ang II–dependent hypertension and whether central and renal T-cell infiltration during Ang II–induced hypertension is sex dependent. Recombinant activating gene-1 (Rag-1)^–/– mice, lacking both T and B cells, were used. Male and female Rag-1^–/– mice received adoptive transfer of male CD3⁺ T cells 3 weeks before 14-day Ang II infusion (490 ng/kg per minute). Blood pressure was monitored via tail cuff. In the absence of T cells, systolic blood pressure responses to Ang II were similar between sexes (Δ22.1 mm Hg males versus Δ18 mmHg females). After adoptive transfer of male T cells, Ang II significantly increased systolic blood pressure in males (Δ37.7 mmHg; PHg). Flow cytometric analysis of total T cells and CD4⁺, CD8⁺, and regulatory Foxp3⁺-CD4⁺ T-cell subsets identified that renal lymphocyte infiltration was significantly increased in males versus females in both control and Ang II–infused animals (P+-positive T cells in the subfornical organ region of the brain was increased in males when compared with that in females. These results suggest that female Rag-1^–/– mice are protected from male T-cell–mediated increases in Ang II–induced hypertension when compared with their male counterparts, and this protection may involve sex differences in the magnitude of T-cell infiltration of the kidney and brain.