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

Maria Chiriaco, Fabio Casciano, Gigliola Di Matteo, Berhard Gentner, Alessia Claps, Silvia Di Cesare, Nicola Cotugno, Patrizia D'Argenio, Paolo Rossi, Alessandro Aiuti, Andrea Finocchi

Research output: Contribution to journalArticle

Abstract

Chronic granulomatous disease (CGD) is a phagocytic disorder characterized by a defective production of reactive oxygen species (ROSs). 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 had a skewed TCRV-beta distribution in CD8+ T cells, particularly in older patients, and a reduced proliferative responses toward mitogens compared to healthy donors (HD). 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 when forcing gp91phox expression transducing T cells from X-CGD and HD with a SIN lentiviral vector (LVV) encoding the gp91phox cDNA.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalClinical Immunology
Volume193
DOIs
Publication statusPublished - Aug 2018

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Chronic Granulomatous Disease
NADPH Oxidase
T-Lymphocytes
Reactive Oxygen Species
Tissue Donors
Granuloma
Autoimmunity
Mitogens
Complementary DNA
Infection
Proteins

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Impaired X-CGD T cell compartment is gp91phox-NADPH oxidase independent. / Chiriaco, Maria; Casciano, Fabio; Di Matteo, Gigliola; Gentner, Berhard; Claps, Alessia; Di Cesare, Silvia; Cotugno, Nicola; D'Argenio, Patrizia; Rossi, Paolo; Aiuti, Alessandro; Finocchi, Andrea.

In: Clinical Immunology, Vol. 193, 08.2018, p. 52-59.

Research output: Contribution to journalArticle

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abstract = "Chronic granulomatous disease (CGD) is a phagocytic disorder characterized by a defective production of reactive oxygen species (ROSs). 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 had a skewed TCRV-beta distribution in CD8+ T cells, particularly in older patients, and a reduced proliferative responses toward mitogens compared to healthy donors (HD). 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 when forcing gp91phox expression transducing T cells from X-CGD and HD with a SIN lentiviral vector (LVV) encoding the gp91phox cDNA.",
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AU - Chiriaco, Maria

AU - Casciano, Fabio

AU - Di Matteo, Gigliola

AU - Gentner, Berhard

AU - Claps, Alessia

AU - Di Cesare, Silvia

AU - Cotugno, Nicola

AU - D'Argenio, Patrizia

AU - Rossi, Paolo

AU - Aiuti, Alessandro

AU - Finocchi, Andrea

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AB - Chronic granulomatous disease (CGD) is a phagocytic disorder characterized by a defective production of reactive oxygen species (ROSs). 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 had a skewed TCRV-beta distribution in CD8+ T cells, particularly in older patients, and a reduced proliferative responses toward mitogens compared to healthy donors (HD). 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 when forcing gp91phox expression transducing T cells from X-CGD and HD with a SIN lentiviral vector (LVV) encoding the gp91phox cDNA.

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