Functional NADPH oxidase 2 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 p67(phox) subunit of NADPH oxidase 2 (NOX2; SSp67phox-/-) attenuates SS hypertension in the Dahl SS rat. We hypothesized that reactive oxygen species produced by NOX2 in T cells drive the SS phenotype and renal damage. T cells were reconstituted by adoptively transferring splenocytes (similar to 10 million) from the Dahl SS (SS -> CD247) rat, the SSp67phox-/- rat (p67(phox)-> CD247), or only PBS (PBS -> CD247) into the SSCD247-/- rat on postnatal day 5. Animals were instrumented with radiotelemeters and studied at 8 wk of age. There were no detectable differences in mean arterial pressure (MAP) or albuminuria between groups when rats were maintained on a low-salt (0.4% NaCl) diet. After 21 days of high-salt diet (4.0% NaCl), MAP and albuminuria were significantly greater in SS -> CD247 rats compared with p67(phox)-> CD247 and PBS -> CD247 rats. Interestingly, there was no difference between p67(phox)-> CD247 and PBS -> CD247 rats in albuminuria or MAP after 21 days. The lack of CD3(+) cells in PBS -> CD247 rats and the presence of CD3(+) cells in rats that received 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 SS -> CD247 and p67(phox)-> CD247 rats. These results indicate that reactive oxygen species produced by NOX2 in T cells participates in the amplification of SS hypertension and renal damage.