Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis of hypertension. Formation of memory T cells, which requires the costimulatory molecule CD70 on antigen-presenting cells, is a cardinal feature of adaptive immunity. Objective: To test the hypothesis that CD70 and immunologic memory contribute to the blood pressure elevation and renal dysfunction mediated by repeated hypertensive challenges. Methods and Results: We imposed repeated hypertensive challenges using either N-nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated angiotensin II stimulation in mice. During these challenges effector memory T cells (T-EM) accumulated in the kidney and bone marrow. In the L-NAME/high-salt model, memory T cells of the kidney were predominant sources of interferon- and interleukin-17A, known to contribute to hypertension. L-NAME/high salt increased macrophage and dendritic cell surface expression of CD70 by 3- to 5-fold. Mice lacking CD70 did not accumulate T-EM cells and did not develop hypertension to either high salt or the second angiotensin II challenge and were protected against renal damage. Bone marrow-residing T-EM cells proliferated and redistributed to the kidney in response to repeated salt feeding. Adoptively transferred T-EM cells from hypertensive mice homed to the bone marrow and spleen and expanded on salt feeding of the recipient mice. Conclusions: Our findings illustrate a previously undefined role of CD70 and long-lived T-EM cells in the development of blood pressure elevation and end-organ damage that occur on delayed exposure to mild hypertensive stimuli. Interventions to prevent repeated hypertensive surges could attenuate formation of hypertension-specific T-EM cells.118812331243NHLBI NIH HHS [R01HL039006, 1F32HL124972-01, F31 HL127986, F32 HL124972, HHSN268201400010C, K01 HL130497, K08 HL121671, P01 HL058000, P01 HL095070, P01HL058000, P01HL095070, R01 HL039006, R01 HL105294, R01 HL108701, R01 HL125865, R01HL105294, R01HL108701]NIGMS NIH HHS [P01 GM015431, P01GM015431, P30 GM103337, T32 GM007569]PHS HHS [HHSN268201400010C
