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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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 15, 2000
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| In: |
The journal of immunology
Year: 2000, Jahrgang: 165, Heft: 8, Pages: 4319-4328 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.165.8.4319 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.165.8.4319 Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/165/8/4319 |
| Verfasserangaben: | Steffen P. Hehner, Raoul Breitkreutz, George Shubinsky, Heike Unsoeld, Klaus Schulze-Osthoff, M. Lienhard Schmitz, and Wulf Dröge |
MARC
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| 520 | |a <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> | ||
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