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. (C) 2018 Elsevier Inc. All rights reserved.

Chiriaco, M., Casciano, F., Di Matteo, G., Gentner, B., Claps, A., Di Cesare, S., et al. (2018). Impaired X-CGD T cell compartment is gp91phox-NADPH oxidase independent. CLINICAL IMMUNOLOGY, 193, 52-59 [10.1016/j.clim.2018.01.010].

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

Casciano F.;Di Matteo G.;Di Cesare S.;Cotugno N.;Rossi P.;Aiuti A.;Finocchi A.
2018-01-01

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. (C) 2018 Elsevier Inc. All rights reserved.
2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
Settore MED/06 - ONCOLOGIA MEDICA
English
Con Impact Factor ISI
CGD; NADPH oxidase; T lymphocytes; TCRV-beta repertoire; gp91phox; Adolescent; Adult; CD8-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Child; Child, Preschool; Granulomatous Disease, Chronic; Humans; Lentivirus; Lymphocyte Activation; Male; NADPH Oxidase 2; NADPH Oxidases; Phagocytosis; Reactive Oxygen Species; Receptors, Antigen, T-Cell, alpha-beta; Young Adult
HEALTH-F5-2010-261387, CELL-PID, the Italian TELETHON foundation (grant number GGP15109), Italian Ministero della Salute (NET- 2011-02350069).
Chiriaco, M., Casciano, F., Di Matteo, G., Gentner, B., Claps, A., Di Cesare, S., et al. (2018). Impaired X-CGD T cell compartment is gp91phox-NADPH oxidase independent. CLINICAL IMMUNOLOGY, 193, 52-59 [10.1016/j.clim.2018.01.010].
Chiriaco, M; Casciano, F; Di Matteo, G; Gentner, B; Claps, A; Di Cesare, S; Cotugno, N; D'Argenio, P; Rossi, P; Aiuti, A; Finocchi, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/227894
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