Sex-specific T-cell regulation of angiotensin II-dependent hypertension.

ABSTRACT: Studies suggest T cells modulate arterial pressure. Because robust sex differences exist in the immune system and in hypertension, we investigated sex differences in T-cell modulation of angiotensin II-induced increases in mean arterial pressure in male (M) and female (F) wild-type and recombination-activating-gene-1-deficient (Rag1(-/-)) mice. Sex differences in peak mean arterial pressure in wild-type were lost in Rag1(-/-) mice (mm Hg: wild-type-F, 136±4.9 versus wild-type-M, 153±1.7; P<0.02; Rag1(-/-)-F, 135±2.1 versus Rag1(-/-)-M, 141±3.8). Peak mean arterial pressure was 13 mm Hg higher after adoptive transfer of male (CD3(M)?Rag1(-/-)-M) versus female (CD3(F)?Rag1(-/-)-M) T cells. CD3(M)?Rag1(-/-)-M mice exhibited higher splenic frequencies of proinflammatory interleukin-17A (2.4-fold) and tumor necrosis factor-? (2.2-fold)-producing T cells and lower plasma levels (13-fold) and renal mRNA expression (2.4-fold) of interleukin-10, whereas CD3(F)?Rag1(-/-)-M mice displayed a higher activation state in general and T-helper-1-biased renal inflammation. Greater T-cell infiltration into perivascular adipose tissue and kidney associated with increased pressor responses to angiotensin II if the T cell donor was male but not female and these sex differences in T-cell subset expansion and tissue infiltration were maintained for 7 to 8 weeks within the male host. Thus, the adaptive immune response and role of pro- and anti-inflammatory cytokine signaling in hypertension are distinct between the sexes and need to be understood to improve therapeutics for hypertension-associated disease in both men and women.

SUBMITTER: Ji H 

PROVIDER: S-EPMC4133294 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature