The phagocyte NADPH oxidase (NOX2) regulates adaptive immune response at the level of both T cells and APCs (138.7)

Abstract

Abstract Absence of phagocyte NADPH oxidase (NOX2) activity causes chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent bacterial infections. In addition to this innate immune dysfunction, CGD patients or animal models display an altered, perhaps augmented, adaptive immune response. It has been previously shown that T cells express the phagocyte oxidase and also been proposed that NOX2 expression alters APC function. The goal of this study was to determine if the differences in adaptive responses are inherent to T cells, or if other cells create an environment that promotes T helper polarization. Anti-CD3 activation of purified naive T cells from NOX2-deficient mice led to augmented IFNγ and IL-17 secretion. NOX2-deficient antigen presenting cells (APC) showed selective increases in GM-CSF, IL-6, TNF and MCP-1 induced by LPS challenge in vitro. APC function was measured using OVA-specific OT-II T cells, and oxidase deficient APC induced more IFNγ and IL-17 upon antigen stimulation. Adoptive transfer of OT-II T cells into wild type or NOX2(-/-) hosts followed by immunization with OVA in the presence of either CFA or Alum revealed altered cytokine profiles of T cells after restimulation in vitro. These results suggest roles for the phagocyte NADPH oxidase in shaping the adaptive and innate immune responses in both a T cell and APC dependent fashion.