Oxygen Radicals Induce Poly(ADP-Ribose) Polymerase-Dependent Cell Death in Cytotoxic Lymphocytes

Thorén, Fredrik B.; Romero, Ana I.; Hellstrand, Kristoffer

doi:10.4049/jimmunol.176.12.7301

Cited by 52 publications

(46 citation statements)

References 44 publications

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“…Our results are in agreement with a recent report showing involvement of AIF in death of CTL in response to reactive oxygen species [23]. Selective release of AIF during AICD of primary CTL was an unexpected finding; however, different laboratories have recently reported that different mitochondrial apoptotic proteins can be selectively released from mitochondria, without cytochrome c, in different cell death systems [24,25].…”

Section: Discussionsupporting

confidence: 93%

Activation‐induced cell death of human melanoma specific cytotoxic T lymphocytes is mediated by apoptosis‐inducing factor

et al. 2006

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Activation-induced cell death (AICD) of T cells can be an impediment towards achieving a robust and long-lived cytolytic T lymphocyte (CTL) response from active specific immunization or after adoptive cell transfer in cancer immunotherapy. The mechanism of AICD in primary CTL, however, remains poorly understood. It is widely believed that AICD is driven by signals from death receptors (DR) and that the cell death takes place in a caspase-dependent manner, although it has been shown that AICD of T cells can be induced by internal triggers and that death takes place in a caspase-independent manner. We show here that AICD in human melanoma epitope-specific primary CTL involves selective mitochondrio-nuclear translocation of the apoptosis inducing factor (AIF) without cytochrome c release, caspase-3 and caspase-8 activation, and results from large-scale DNA fragmentation. The c-jun-N terminal kinase (JNK) inhibitor, SP600125, blocks the mitochondrio-nuclear translocation of AIF and prevents AICD in these CTL. These findings suggest that the AICD in human melanoma epitope specific primary CTL is mediated by mitochondrial AIF release and JNK is involved in regulation of this death process.

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Section: Discussionsupporting

confidence: 93%

Activation‐induced cell death of human melanoma specific cytotoxic T lymphocytes is mediated by apoptosis‐inducing factor

et al. 2006

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“…After overnight incubation, lymphocytes were assayed for end-stage, oxidant-induced cell death by using flow cytometry based on the altered characteristics displayed by end-stage apoptotic cells, i.e., a reduced forward scatter and an increased right angle scatter (16). Apoptosis was confirmed using annexin V staining as described elsewhere (18). In some experiments, lymphocytes were exposed to MPs that were stimulated with the formylated bacterial peptide fMLF (0.1 M) or yeast cells (MP/yeast ratio of 1:4).…”

Section: Lymphocyte Cell Deathmentioning

confidence: 99%

“…After centrifugation at 380 ϫ g for 15 min, mononuclear cells were collected at the interface. The mononuclear cells were further separated into lymphocytes and MPs using a countercurrent centrifugal elutriation technique as described elsewhere (18). In brief, cells were fed into an ultracentrifuge at 2100 rpm, where the sedimentation rate of cells is balanced by a counter-directed flow through the chamber.…”

Section: Cellsmentioning

confidence: 99%

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Cutting Edge: Antioxidative Properties of Myeloid Dendritic Cells: Protection of T Cells and NK Cells from Oxygen Radical-Induced Inactivation and Apoptosis

Thorén

Betten

Romero

et al. 2007

The Journal of Immunology

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Dendritic cells (DCs) communicate with nonadaptive and adaptive lymphocytes on multiple levels. Efficient DC-lymphocyte interactions require that lymphocytes remain viable and functional also under conditions of oxidative stress, such as in microbial infection or in the malignant microenvironment. For this study, we exposed human T and NK cells to oxidants delivered either by autologous phagocytes or in the form of exogenous hydrogen peroxide. In accordance with earlier studies, these lymphocytes became dysfunctional and subsequently apoptotic. The presence of myeloid DCs efficiently rescued T cells (CD4+ and CD8+) and NK cells from oxidant-induced inactivation and apoptosis. The mechanism of the myeloid DC-mediated lymphocyte protection was, at least in part, explained by the capacity of the myeloid DCs to neutralize extracellular oxygen radicals, which, in turn, was reversible upon coincubation with a catalase inhibitor. Our results are suggestive of a novel aspect of DC-lymphocyte interaction that may have implications for lymphocyte function in inflamed tissue.

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“…ROS are antimicrobial substances that kill ingested microbes, but they may also compromise the function and viability of adjacent cells when released into the extracellular space (4,5). For example, T cells and other lymphocytes rapidly become inactivated and eventually undergo apoptosis when exposed to ROS (6)(7)(8)(9). Because effector T cells commonly exert their functions in the oxidative environment characteristic of infected or inflamed tissues (10,11), it is conceivable that T cells use strategies to escape oxygen radical-induced inactivation.…”

mentioning

confidence: 99%

Redox Remodeling by Dendritic Cells Protects Antigen-Specific T Cells against Oxidative Stress

Martner

Aurelius

Rydström

et al. 2011

The Journal of Immunology

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Microorganisms and microbial products induce the release of reactive oxygen species (ROS) from monocytes and other myeloid cells, which may trigger dysfunction and apoptosis of adjacent lymphocytes. Therefore, T cell-mediated immunity is likely to comprise mechanisms of T cell protection against ROS-inflicted toxicity. The present study aimed to clarify the dynamics of reduced sulfhydryl groups (thiols) in human T cells after presentation of viral and bacterial Ags by dendritic cells (DCs) or B cells. DCs, but not B cells, efficiently triggered intra- and extracellular thiol expression in T cells with corresponding Ag specificity. After interaction with DCs, the Ag-specific T cells acquired the capacity to neutralize exogenous oxygen radicals and resisted ROS-induced apoptosis. Our results imply that DCs provide Ag-specific T cells with antioxidative thiols during Ag presentation, which suggests a novel aspect of DC/T cell cross-talk of relevance to the maintenance of specific immunity in inflamed or infected tissue.

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Oxygen Radicals Induce Poly(ADP-Ribose) Polymerase-Dependent Cell Death in Cytotoxic Lymphocytes

Cited by 52 publications

References 44 publications

Activation‐induced cell death of human melanoma specific cytotoxic T lymphocytes is mediated by apoptosis‐inducing factor

Activation‐induced cell death of human melanoma specific cytotoxic T lymphocytes is mediated by apoptosis‐inducing factor

Cutting Edge: Antioxidative Properties of Myeloid Dendritic Cells: Protection of T Cells and NK Cells from Oxygen Radical-Induced Inactivation and Apoptosis

Redox Remodeling by Dendritic Cells Protects Antigen-Specific T Cells against Oxidative Stress

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