Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol Pool

• Verfasst von: Hehner, Steffen Peter [VerfasserIn]
• Verfasst von: Schulze-Osthoff, Klaus [VerfasserIn]
• Verfasst von: Dröge, Wulf [VerfasserIn]
• Titel: Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol Pool
• Verf.angabe: Steffen P. Hehner, Raoul Breitkreutz, George Shubinsky, Heike Unsoeld, Klaus Schulze-Osthoff, M. Lienhard Schmitz, and Wulf Dröge
• E-Jahr: 2000
• Jahr: October 15, 2000
• Umfang: 11 S.
• Fussnoten: Gesehen am 03.02.2021
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2000
• Band/Heft Quelle: 165(2000), 8, Seite 4319-4328
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.165.8.4319
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 174720627X

Abstract

<p>Exposure of T cells to the macrophage products hydrogen peroxide (HP) or l-lactate (LAC) was previously shown to enhance IL-2 production and to modulate glutathione (GSH) status. We now found that 50 μM HP and 30 mM LAC enhanced strongly the transcription from the IL-2 promoter in Jurkat T cells after stimulation with anti-CD28 together with or without anti-CD3 but not with anti-CD3 Abs alone. Therefore, we used anti-CD3 plus anti-CD28-stimulated cells to investigate the effect of the GSH reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on the signal cascade. BCNU enhanced the transcription to a similar extent as HP or LAC. Lowering the intracellular GSH/GSH disulfide ratio by BCNU, HP, or NO resulted in all cases in the fulminant enhancement of Jun-N-terminal kinase and p38 mitogen-activated protein kinase but not extracellular signal-regulated kinase 1/2. Jun-N-terminal kinase and NF-κB activation was enhanced through pathways involving Rac, Vav1, PKCΘ, p56^lck, p59^fyn, and IκB kinases. In a cell-free system, the autophosphorylation of rFyn was stimulated by GSH disulfide but not by HP. These findings suggest that the oxidation of the cellular thiol pool may play a role as an amplifying mechanism for TCR/CD3 signals in immune responses.</p>