CD70 Exacerbates Blood Pressure Elevation and Renal Damage in Response to Repeated Hypertensive Stimuli
Rationale: 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 co-stimulatory molecule CD70 on antigen presenting cells, is a cardinal feature of adaptive immunity.
Objective: To test the hypothesis that CD70 and immunological 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 L-NAME/high salt or repeated ang II stimulation in mice. During these challenges effector memory T (TEM) cells accumulated in the kidney and bone marrow. In the L-NAME/high salt model, memory T cells of the kidney were predominant sources of IFN-γ and IL-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 TEM cells and did not develop hypertension to either high salt or the second ang II challenge and were protected against renal damage. Bone marrow residing TEM cells proliferated and redistributed to the kidney in response to repeated salt feeding. Adoptively transferred TEM cells from hypertensive mice homed to the bone marrow and spleen and expanded upon salt feeding of the recipient mice.
Conclusions: Our findings illustrate a previously undefined role of CD70 and long-lived TEM cells in the development of blood pressure elevation and end-organ damage that occur upon delayed exposure to mild hypertensive stimuli. Interventions to prevent repeated hypertensive surges could attenuate formation of hypertension-specific TEM cells.
- adaptive immunity
- interferon gamma
- immunological memory
- immune system
- bone marrow
- Received December 2, 2015.
- Revision received March 15, 2016.
- Accepted March 17, 2016.