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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 mm : Hg females). After adoptive transfer of male T cells, Ang II significantly increased systolic blood pressure in males (Δ37.7 mm : Hg; P&lt;0.05) when compared with females (Δ13.7 mm : Hg). 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&lt;0.05). Immunohistochemical staining for CD3(+)-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.

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