Functional NADPH oxidase 2 (NOX2) in T cells amplifies salt-sensitive hypertension and associated renal damage.

Infiltrating T cells in the kidney amplify salt sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells (SSCD247-/- ) or of the p67phox subunit of NOX2 (SSp67phox-/- ) attenuates salt-sensitive hypertension in the Dahl SS rat. We hypothesized that reactive oxygen species (ROS) produced by NOX2 in T-cells drive the SS phenotype and renal damage. T cells were reconstituted by adoptively transferring splenocytes (~10 million) from the Dahl SS (SS→CD247), the SSp67phox-/- (p67phox→CD247) or of only PBS (PBS→CD247) into the SSCD247-/- rat on postnatal day 5. Animals were instrumented with radiotelemeters and studied at 8 weeks of age. There were no detectable difference in mean arterial pressure (MAP) or albuminuria between groups when the rats were maintained on a low salt (LS, 0.4% NaCl) diet. After 21 days of high salt (HS, 4.0% NaCl), MAP and albuminuria were significantly greater in the SS→CD247 compared to the p67phox→CD247 rats and the PBS→CD247 rats. Interestingly, there was no difference between p67phox→CD247 and PBS→CD247 in albuminuria or MAP after 21 days. The lack of CD3+ cells in the PBS→CD247 but presence of CD3+ cells in rats receiving the T cell transfer demonstrated the effectiveness of the adoptive transfer. No differences in the number of CD3+, CD4+, or CD8+ cells were observed in the kidneys of the SS→CD247 and p67phox→CD247 rats. These results indicate that ROS production by T cells participates in the amplification of salt-sensitive hypertension and renal damage.