T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation

Jackson, Sharon H.; Devadas, Satish; Kwon, Jaeyul; Pinto, Lígia A.; Williams, Mark S.

doi:10.1038/ni1096

Cited by 416 publications

(443 citation statements)

References 50 publications

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“…This was first suggested by initial observations that H 2 O 2 can mimic antigen receptor stimulation, by negatively regulating the SH2 domain-containing PTPs, SHP-1 and SHP-2 (170). Subsequent studies confirmed that T cells express essential NADPH oxidase (NOX2) components, which contribute to oxidant production and signaling upon T cell receptor (TCR) activation, thereby regulating inflammatory cytokine production and T cell adhesion (47,171). Similarly, antigen receptor stimulation in B cells has been found to involve the activation of NADPH oxidase, which serves to amplify BCR signaling by inactivation of the tyrosine phosphatase SHP-1, thereby promoting the activation of the protein tyrosine kinase Syk (170).…”

Section: Nox-mediated Signaling In Inflammatory-immune Cellsmentioning

confidence: 96%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

187

192

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The deliberate production of reactive oxygen species (ROS) by phagocyte NADPH oxidase is widely appreciated as a critical component of antimicrobial host defense. Recently, additional homologs of NADPH oxidase (NOX) have been discovered throughout the animal and plant kingdoms, which appear to possess diverse functions in addition to host defense, including cell proliferation, differentiation, and regulation of gene expression. Several of these NOX homologs are also expressed within the respiratory tract, where they participate in innate host defense as well as in epithelial and inflammatory cell signaling and gene expression, and fibroblast and smooth muscle cell proliferation, in response to bacterial or viral infection and environmental stress. Inappropriate expression or activation of NOX/DUOX during various lung pathologies suggests their specific involvement in respiratory disease. This review summarizes the current state of knowledge regarding the general functional properties of mammalian NOX enzymes, and their specific importance in respiratory tract physiology and pathology.

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Section: Nox-mediated Signaling In Inflammatory-immune Cellsmentioning

confidence: 96%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

187

192

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“…An intact Txn system may be necessary to attenuate signaling by surface receptors. In response to ligand binding, NADPH-oxidase enzymes associated with the cytosolic aspect of growth factor receptors generate H 2 O 2 [22][23][24]26,[75][76][77][78][79][80][81][82][83]. A conserved catalytic cysteine at the active site of protein tyrosine phosphatases is oxidized by H 2 O 2 to a sulfenic acid, which further reacts with a backbone nitrogen to form a sulfenylamide [68].…”

Section: Effects On Signalingmentioning

confidence: 99%

“…In addition to its general roles, Txnrd1-dependent reduction reactions are important in specific cells or situations for limiting signal transduction from several cell surface receptors, including the T cell receptor, the insulin receptor, and the epidermal growth factor receptor [21][22][23][24][25][26][27]. Txn1 is also required for DNA-binding activity of the transcription factors NFκB, AP1, steroid hormone receptors, and p53 [1,[28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

Bondareva¹,

Capecchi²,

Iverson³

et al. 2007

Free Radical Biology and Medicine

102

115

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Thioredoxin reductases (Txnrd)1 maintain intracellular redox homeostasis in most organisms. Metazoans Txnrds also participate in signal transduction. Mouse embryos homozygous for a targeted null mutation of the txnrd1 gene, encoding the cytosolic thioredoxin reductase, were viable at embryonic day 8.5 (E8.5) but not at E9.5. Histology revealed that txnrd1 −/− cells were capable of proliferation and differentiation; however, mutant embryos were smaller than wild-type littermates and failed to gastrulate. In situ marker gene analyses indicated primitive streak mesoderm did not form. Microarray analyses on E7.5 txnrd −/− and txnrd +/+ littermates showed similar mRNA levels for peroxiredoxins, glutathione reductases, mitochondrial Txnrd2, and most markers of cell proliferation. Conversely, mRNAs encoding sulfiredoxin, IGF-binding protein 1, carbonyl reductase 3, glutamate cysteine ligase, glutathione S-transferases, and metallothioneins were more abundant in mutants. Many gene expression responses mirrored those in thioredoxin reductase 1-null yeast; however mice exhibited a novel response within the peroxiredoxin catalytic cycle. Thus, whereas yeast induce peroxiredoxin mRNAs in response to thioredoxin reductase disruption, mice induced sulfiredoxin mRNA. In summary, Txnrd1 was required for correct patterning of the early embryo and progression to later development. Conserved responses to Txnrd1 disruption likely allowed proliferation and limited differentiation of the mutant embryo cells.

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“…This result was consistent with an earlier report that PHA and PMA induce oxidative product formation in the Jurkat malignant T cell line (12). Although the intracellular source of ROI production in T cells is still being investigated, studies have implicated the mitochondria as well as a phagocyte-type NADPH oxidase as contributors (13)(14)(15)(16)). An essential role for ROI in T cell function was initially demonstrated by reports indicating that antioxidants inhibit proliferation and IL-2 production when administered during the early stages of T cell activation (17,18).…”

mentioning

confidence: 99%

The Requirement of Reversible Cysteine Sulfenic Acid Formation for T Cell Activation and Function

Michalek

Nelson

Holbrook

et al. 2007

The Journal of Immunology

101

102

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Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in mediating cellular responses. We have examined the importance of reversible cysteine sulfenic acid formation in naive CD8+ T cell activation and proliferation. We observed that, within minutes of T cell activation, naive CD8+ T cells increased ROI levels in a manner dependent upon Ag concentration. Increased ROI resulted in elevated levels of cysteine sulfenic acid in the total proteome. Analysis of specific proteins revealed that the protein tyrosine phosphatases SHP-1 and SHP-2, as well as actin, underwent increased sulfenic acid modification following stimulation. To examine the contribution of reversible cysteine sulfenic acid formation to T cell activation, increasing concentrations of 5,5-dimethyl-1,3-cyclohexanedione (dimedone), which covalently binds to cysteine sulfenic acid, were added to cultures. Subsequent experiments demonstrated that the reversible formation of cysteine sulfenic acid was critical for ERK1/2 phosphorylation, calcium flux, cell growth, and proliferation of naive CD8+ and CD4+ T cells. We also found that TNF-α production by effector and memory CD8+ T cells was more sensitive to the inhibition of reversible cysteine sulfenic acid formation than IFN-γ. Together, these results demonstrate that reversible cysteine sulfenic acid formation is an important regulatory mechanism by which CD8+ T cells are able to modulate signaling, proliferation, and function.

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T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation

Cited by 416 publications

References 50 publications

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

The Requirement of Reversible Cysteine Sulfenic Acid Formation for T Cell Activation and Function

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