Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension

Abstract

Objective - Survival of immune and nonimmune cells relies on Axl, a receptor tyrosine kinase, which is implicated in hypertension. Activated T lymphocytes are involved in regulation of high blood pressure. The goal of the study was to investigate the role of Axl in T-lymphocyte functions and its contribution to salt-dependent hypertension. Approach and Results - We report increased apoptosis in peripheral blood from Axl -/- mice because of lower numbers of white blood cells mostly lymphocytes. In vitro studies showed modest reduction in interferon gamma production in Axl -/- type 1 T helper cells. Axl did not affect basic proliferation capacity or production of interleukin 4 in Axl -/- type 2 T helper cells. However, competitive repopulation of Axl -/- bone marrow or adoptive transfer of Axl -/- CD4 + T cells to Rag1 -/- mice showed robust effect of Axl on T lymphocyte expansion in vivo. Adoptive transfer of Axl -/- CD4 + T cells was protective in a later phase of deoxycorticosterone-acetate and salt hypertension. Reduced numbers of CD4 + T cells in circulation and in perivascular adventitia decreased vascular remodeling and increased vascular apoptosis in the late phase of hypertension. Conclusions - These findings suggest that Axl is critical for survival of T lymphocytes, especially during vascular remodeling in hypertension.