Impaired X-CGD T cell compartment is gp91phox-NADPH oxidase independent

Chronic granulomatous disease (CGD) is a phagocytic disorder characterized by a defective production of reactive oxygen species (ROS). Although infections and granuloma formation are the most common manifestations in CGD patients, a significant number of patients experienced autoimmunity and inflammatory diseases suggesting that adaptive immune abnormalities might be involved. Here we investigated T-cell compartment and showed that CGD patients respect to healthy donor (HD), had a skewed TCRV-beta distribution in CD8+ T cells, particularly in older patients, and a reduced proliferative responses toward mitogens. Afterwards we studied the role of gp91phox protein in causing these alterations and demonstrated that human T cells do not express gp91phox and TCR-stimulated ROS generation is gp91phox-NADPH oxidase independent. Finally, we proved that the NADPH oxidase is not active in the T cell compartment even forcing gp91phox expression transducing T cells from X-CGD and HD with a SIN lentiviral vector (LVV) expressing the gp91phox cDNA.