Abstract 008: Sex-dependency Of T Cell-induced Salt-sensitive Hypertension And Kidney Damage

We have previously demonstrated that female Dahl Salt-Sensitive (SS) rats are protected from salt-induced hypertension and renal injury compared to males. There is an immunological component to this sex difference, since genetic deletion of T cells via mutation of the CD247 gene on the Dahl SS genetic background (CD247-/-) normalizes sex differences in blood pressure, though females are still protected from salt-sensitive renal damage compared to males. The current study hypothesized that sex of the T cell is an important factor in determining the severity of salt-sensitivity. We tested the hypothesis via a sex-specific splenocyte transfer by freshly isolating 10 7 male or female splenocytes and injecting them i.p. on postnatal day 5 into either male or female CD247-/- recipients. At 9 weeks of age, rats underwent a 3 week high salt challenge (HS, 4.0% NaCl, AIN-76A), with blood pressure measured continuously by telemetry and overnight urine collected weekly to assess renal damage. All data presented are from HS day 21. Transfer of either male or female donor splenocytes into CD247-/- recipient males exacerbated salt-induced hypertension compared to PBS vehicle controls (+PBS: 143.7±2.9, +Male: 152.8±5.2, +Female: 151.8±3.9 mmHg, n=11-14, p<0.05). Similarly reflected in proteinuria, splenocyte transfer, regardless of sex, also worsened kidney damage in male CD247-/- recipients (+PBS: 191.9±26.7, +Male: 304.6±51.3, +Female: 283.9±37.1 mg/day, n=12-16, p<0.05). In CD247-/- female recipients, there was an exacerbation in blood pressure with the transfer of male splenocytes (+PBS: 144.8±6.1, +Male: 151.5±3.9 mmHg, n=6-13, p<0.05), but no significant change with the transfer of female splenocytes (+Female: 145.3±2.6 mmHg). There was a trend for male splenocytes to worsen proteinuria in CD247-/- female recipients (+PBS: 103.9±11.1, +Male: 157.7±21.2 mg/day, n=6-14, p=0.056), but there was a significant reduction in the transfer of female versus male splenocytes (+Female: 113.2±15.7, p<0.05). Through flow cytometry, we confirmed similar extent of T cell reconstitution in both male and female CD247-/- recipients. These data demonstrate that salt-sensitive hypertension and renal damage are amplified if the sex of the T cell or the recipient are male.