NADPH Oxidase 2-Derived Reactive Oxygen Species Promote CD8+ T Cell Effector Function
Copyright © 2024 by The American Association of Immunologists, Inc..
Oxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+ CTLs. However, the molecular mechanisms impacting CD8+ T cell function remain unknown. In the present study, we examined the role of NOX2 in both NOD mouse and human CD8+ T cell function. Genetic ablation or chemical inhibition of NOX2 in CD8+ T cells significantly suppressed activation-induced expression of the transcription factor T-bet, the master transcription factor of the Tc1 cell lineage, and T-bet target effector genes such as IFN-γ and granzyme B. Inhibition of NOX2 in both human and mouse CD8+ T cells prevented target cell lysis. We identified that superoxide generated by NOX2 must be converted into hydrogen peroxide to transduce the redox signal in CD8+ T cells. Furthermore, we show that NOX2-generated oxidants deactivate the tumor suppressor complex leading to activation of RheB and subsequently mTOR complex 1. These results indicate that NOX2 plays a nonredundant role in TCR-mediated CD8+ T cell effector function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:212 |
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| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 212(2024), 2 vom: 15. Jan., Seite 258-270 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Jing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2024 Date Revised 10.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.4049/jimmunol.2200691 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Oxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+ CTLs. However, the molecular mechanisms impacting CD8+ T cell function remain unknown. In the present study, we examined the role of NOX2 in both NOD mouse and human CD8+ T cell function. Genetic ablation or chemical inhibition of NOX2 in CD8+ T cells significantly suppressed activation-induced expression of the transcription factor T-bet, the master transcription factor of the Tc1 cell lineage, and T-bet target effector genes such as IFN-γ and granzyme B. Inhibition of NOX2 in both human and mouse CD8+ T cells prevented target cell lysis. We identified that superoxide generated by NOX2 must be converted into hydrogen peroxide to transduce the redox signal in CD8+ T cells. Furthermore, we show that NOX2-generated oxidants deactivate the tumor suppressor complex leading to activation of RheB and subsequently mTOR complex 1. These results indicate that NOX2 plays a nonredundant role in TCR-mediated CD8+ T cell effector function | ||
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| 700 | 1 | |a Chernatynskaya, Anna V |e verfasserin |4 aut | |
| 700 | 1 | |a Newby, Brittney |e verfasserin |4 aut | |
| 700 | 1 | |a Brusko, Todd M |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Barra, Jessie M |e verfasserin |4 aut | |
| 700 | 1 | |a Morgan, Nadine |e verfasserin |4 aut | |
| 700 | 1 | |a Santarlas, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Reeves, Westley H |e verfasserin |4 aut | |
| 700 | 1 | |a Tse, Hubert M |e verfasserin |4 aut | |
| 700 | 1 | |a Leiding, Jennifer W |e verfasserin |4 aut | |
| 700 | 1 | |a Mathews, Clayton E |e verfasserin |4 aut | |
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