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

<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...

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Main Authors: Hehner, Steffen Peter (Author) , Schulze-Osthoff, Klaus (Author) , Dröge, Wulf (Author)
Format: Article (Journal)
Language:English
Published: October 15, 2000
In: The journal of immunology
Year: 2000, Volume: 165, Issue: 8, Pages: 4319-4328
ISSN:1550-6606
DOI:10.4049/jimmunol.165.8.4319
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.165.8.4319
Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/165/8/4319
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Author Notes:Steffen P. Hehner, Raoul Breitkreutz, George Shubinsky, Heike Unsoeld, Klaus Schulze-Osthoff, M. Lienhard Schmitz, and Wulf Dröge
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Summary:<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<sup>lck</sup>, p59<sup>fyn</sup>, 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>
Item Description:Gesehen am 03.02.2021
Physical Description:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.165.8.4319

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