Abstract 240: A Potential Role of Memory T cells in Hypertension

Abstract

Immunological memory is an important component of the adaptive immune response to pathogenic stimuli. Effector memory T cells, which are CD44high CD62Llow, reside in various non-lymphoid tissues and serve as a first line defense against foreign antigens. We have previously shown that T cells are important in hypertension, but the role of memory T cells has not been defined. Thus we hypothesized that CD8+ memory T cells are component of this memory response. To test this hypothesis, mice initially received two weeks of ang II, were allowed to recover for 3 weeks and were then re-infused with low dose of ang II (140 ng/kg/min) that minimally raises blood pressure in naïve mice. This low-dose of ang II increased blood pressure to 137±6 mmHg in mice that had previously received a vehicle infusion, but to 172±12 mmHg in mice that had received ang II. In keeping with a memory T cell response, we found that angiotensin II causes a 5 to 10-fold increase in CD8+ CD62Lhigh/CD44high/CCR7+ central memory cells in the kidney while reducing these effector memory CD8+ T cells in the spleen. CD8+ memory T cells require co-stimulatory signaling between CD70 on macrophages and CD27 on T cells. We found that angiotensin II infusion increased CD70 mRNA in isolated kidney vessels by 5 to 10-fold. Similarly, flow cytometry revealed that angiotensin II increased macrophages expressing CD70 and CD8+ T cells expressing CD27 expression in the kidney. Thus, these studies indicate that repeated exposures to angiotensin II promote an immune memory response of CD8+ T cells and markedly enhance the hypertensive response to this octapeptide. The role of CD27 and CD70 signaling requires additional study but might serve as a therapeutic target.