TY  - BOOK
AU  - Umans, Jason G
TI  - Sex-specific T-cell regulation of angiotensin II-dependent hypertension
SN  - 0194-911X
PY  - 2014///
KW  - *Angiotensin II/ae [Adverse Effects]
KW  - *Hypertension/ci [Chemically Induced]
KW  - *Hypertension/pp [Physiopathology]
KW  - *T-Lymphocytes/pa [Pathology]
KW  - *T-Lymphocytes/ph [Physiology]
KW  - Adaptive Immunity/ph [Physiology]
KW  - Angiotensin II/pd [Pharmacology]
KW  - Animals
KW  - Blood Pressure/de [Drug Effects]
KW  - Blood Pressure/ph [Physiology]
KW  - Disease Models, Animal
KW  - Female
KW  - Heart Rate/de [Drug Effects]
KW  - Heart Rate/ph [Physiology]
KW  - Homeodomain Proteins/ge [Genetics]
KW  - Homeodomain Proteins/ph [Physiology]
KW  - Hypertension/pa [Pathology]
KW  - Interleukin-10/me [Metabolism]
KW  - Interleukin-17/me [Metabolism]
KW  - Male
KW  - Mice
KW  - Mice, Knockout
KW  - Sex Factors
KW  - Tumor Necrosis Factor-alpha/me [Metabolism]
KW  - MedStar Health Research Institute
KW  - Comparative Study
KW  - Journal Article
KW  - Research Support, N.I.H., Extramural
KW  - Research Support, Non-U.S. Gov't
N1  - Available online from MWHC library: 1979 - present
N2  - 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-alpha (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.  2014 American Heart Association, Inc
UR  - http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03663
ER  -