Abstract Body: Salt-Sensitive (SS) hypertension and renal damage in the Dahl SS rat mirrors human disease with T cell infiltration in the kidney accompanying the development of SS hypertension and renal damage. Deletion of T cells on the Dahl SS genetic background (SS^CD247-/-) attenuates hypertension and renal damage, and subsequent replacement of CD4+ T cells alone restores the disease phenotype while the transfer of only CD8+ T cells had no significant effect on the disease phenotype. The present study tested the hypothesis that CD4+ and CD8+ T cells will synergistically act to enhance salt-sensitive hypertension and renal damage in the Dahl SS compared to the injection of only CD4+ T cells. This hypothesis was tested by adoptive transferring purified CD4+ T cells from Dahl SS (~5 million, CD4+ SS→), a combination of ~5 million CD4+ T cells with ~5 million CD8+ T cells from Dahl SS (CD4+CD8+ SS→) or PBS vehicle (PBS→) into the SS^CD247-/- rat on postnatal day 5. Animals were instrumented with radiotelemeters at 8 weeks of age. After a week of recovery, baseline measurements of blood pressure and albumin excretion were obtained while rats were fed a low salt (LS, 0.4% NaCl) diet. Rats were then switched to a high salt (HS, 4.0% NaCl) diet for 21 days, with continuous blood pressure measurements and urine collections every 7 days. On day 21, the rats were euthanized, and their kidneys were perfused and collected for immune cell analysis by flow cytometry. During the LS baseline period there was no significant difference observed in mean arterial pressure (MAP) between the CD4+ SS→, CD4+CD8+ SS→, or PBS→ groups (121±2, 122±2, 119±1 mmHg; n=9, 10, 6, respectively). After three weeks of HS, both CD4+ SS→ and CD4+CD8+ SS→ rats demonstrated an equivalent amplification of SS hypertension (176±6 and 179±5 mmHg) and albuminuria (261±53 and 285±37 mg/day, respectively) which was significantly greater than the MAP (159±5 mmHg) and albuminuria (169±29 mg/day) in PBS→. Finally, a flow cytometric analysis at the end of the experiment confirmed the absence of CD3+ T cells in the PBS→ and documented the reconstitution of equal numbers of CD4+ cells in the blood and kidney of the rats receiving CD4+ cells or the combined CD4+ CD8+ cell transfer. We also confirmed the CD4+CD8+ was the only group that had reconstituted CD8+ T cells. These studies demonstrated that CD4+ T cells amplify salt-sensitive hypertension and renal damage in the Dahl SS independently from CD8+ T cells.