Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation

Chaudhri, G; Clark, I A; Hunt, N H; Cowden, W B; Ceredig, R

doi:10.4049/jimmunol.137.8.2646

Cited by 139Redox biology and oxidative stressT-cell and B-cell ImmunologyNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation

Chaudhri, G, Clark, I A, Hunt, N H, Cowden, W B, Ceredig, R·1986·The Journal of Immunology

DOI 10.4049/jimmunol.137.8.2646

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Abstract

Because oxygen-centered free radicals are involved in cell-mediated immune responses, we examined the possibility that these reactive species could also have a role in the lymphoproliferative response to alloantigens in the mixed lymphocyte culture (MLC). Three classes of agents that prevent the formation, or damaging effects, of oxygen radicals were tested: the non-permeant electron acceptor ferricyanide; the iron chelators desferrioxamine, desferrithiocin, octanohydroxamic acid, and pyridoxal isonicotinoyl hydrazone, which are thought to be capable of preventing the iron-catalyzed reduction of H2O2 to more reactive species; and the lipid-soluble free radical scavenger butylated hydroxyanisole. These compounds inhibited the proliferation of all potential responder cells in the MLC in a dose-dependent manner. Inhibition was observed only if these agents were present early (less than 40 hr) in the MLC; if added later, their effects were significantly reduced. In contrast, the interleukin 2 (IL 2)-dependent proliferation of CTLL-2 cells or Con A blasts was not affected by these compounds at concentrations that inhibited proliferation in MLC by greater than 90%. Interleukin 1 (IL 1) production by peritoneal exudate cells and IL 2 and IL 1 levels in MLC were not affected by any of the agents tested. By flow microfluorometry, the expression of IL 2 receptors on stimulated T cells was found to be inhibited in the presence of these drugs. Taken together, the data point to an important role for free radical-mediated processes during the early stages of T lymphocyte activation, before IL 2 receptor expression.

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Dröge, W., Schulze‐Osthoff, K., Mihm, S., Galter, D., Schenk, H., Eck, H., Roth, S., & Gmünder, H. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.14.7958618 · Cited by 444 · see citing works
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Sandstrom, P. A., Tebbey, P. W., Cleave, S. V., & Buttke, T. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42178-8 · Cited by 205 · see citing works
Free Radicals and the Regulation of Mammalian Cell Proliferation
Burdo, R. H., & Rice-Evans, C. A. (1989) · Free Radical Research Communications · doi:10.3109/10715768909087918 · Cited by 191 · see citing works
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Sandstrom, P. A., & Buttke, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4708 · Cited by 186 · see citing works
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Herrlich, P. A., Ponta, H., & Rahmsdorf, H. J. (1992) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/3540551921_7 · Cited by 180 · see citing works
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Yang, C., Wu, S., Mou, Z., Zhou, Q., Dai, X., Ou, Y., Chen, X., Chen, Y., Xu, C., Hu, Y., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.022 · Cited by 178 · see citing works
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Cho, Y. S., & Moon, H. (2010) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2010.2.3.183 · Cited by 175 · see citing works
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Williams, M. S., & Kwon, J. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.05.029 · Cited by 167 · see citing works
Human immunodeficiency virus type 1–infected monocytic cells can destroy human neural cells after cell‐to‐cell adhesion
Tardieu, M., Héry, C., Peudenier, S., et al. (1992) · Annals of Neurology · doi:10.1002/ana.410320104 · Cited by 160 · see citing works
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Delmastro-Greenwood, M. M., & Piganelli, J. D. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/593863 · Cited by 129 · see citing works
“supported our experimentation by demonstrating attenuation of Tcell proliferation and IL-2R expression following antioxidant treatment [186, 187].”
Background
Cell proliferation, cell death and aging
Franceschi, C. (1989) · Aging Clinical and Experimental Research · doi:10.1007/bf03323871 · Cited by 128 · see citing works
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Michalek, R. D., Nelson, K. J., Holbrook, B. C., Yi, J. S., Stridiron, D., Daniel, L. W., Fetrow, J. S., King, S. B., Poole, L. B., & Grayson, J. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6456 · Cited by 112 · see citing works
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Lawrence, D. A., Song, R., & Webert, P. (1996) · Journal of Leukocyte Biology · doi:10.1002/jlb.60.5.611 · Cited by 102 · see citing works
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Walsh, C. M., & Edinger, A. L. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00919.x · Cited by 99 · see citing works
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Burne-Taney, M. J., & Rabb, H. (2003) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200301000-00014 · Cited by 93 · see citing works
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Herbel, C., Patsoukis, N., Bardhan, K., Seth, P., Weaver, J. D., & Boussiotis, V. A. (2016) · Clinical and Translational Medicine · doi:10.1186/s40169-016-0110-9 · Cited by 93 · see citing works
In vivo T Cell Activation in Lymphoid Tissues is Inhibited in the Oxygen-Poor Microenvironment
Ohta, A., Diwanji, R., Kini, R., Subramanian, M., Ohta, A., & Sitkovsky, M. V. (2011) · Frontiers in Immunology · doi:10.3389/fimmu.2011.00027 · Cited by 86 · see citing works
“Treatment of T cells with Co2+ or desferrioxamine, which are often used to mimic hypoxia, also reduced T cell activation (Lederman et al., 1984; Carotenuto et al., 1986; Chaudhri et al., 1986; Wang et al., 1996; Pae et al., 2004).”
Background
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Hildeman, D. A. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.03.023 · Cited by 88 · see citing works
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Macintyre, A. N., & Rathmell, J. C. (2013) · Cancer & Metabolism · doi:10.1186/2049-3002-1-5 · Cited by 87 · see citing works
“While some degree of ROS is beneficial for both T cell activation [55] and tumor development [56], excessive ROS leads to oxidative organelle”
Background
A common mitochondrial haplogroup is associated with elevated total serum IgE levels
Raby, B. A., Klanderman, B. J., Murphy, A., Mazza, S., Camargo, C. A., Silverman, E. K., & Weiss, S. T. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.05.029 · Cited by 83 · see citing works
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Fidelus, R. K. (1988) · Cellular Immunology · doi:10.1016/0008-8749(88)90015-9 · Cited by 79 · see citing works
A new lease of life for an old enzyme
Martini, G., & Ursini, M. V. (1996) · BioEssays · doi:10.1002/bies.950180806 · Cited by 79 · see citing works
Redox Signaling, Neuroinflammation, and Neurodegeneration
Aguilera, G., Colín-González, A. L., Rangel‐López, E., Chavarría, A., & Santamarı́a, A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7099 · Cited by 79 · see citing works
“…culture, iron chelators and a lipid-soluble free radical scavenger prevented the iron-catalyzed reduction of H 2 O 2 to OH, and they inhibited the cellular proliferation, demonstrating that ROS are positive mediators during early stages of T lymphocyte activation and proliferation (28, 29).”
High rates of extracellular superoxide generation by cultured human fibroblasts: involvement of a lipid-metabolizing enzyme
O’Donnell, V. B., & Azzi, A. (1996) · Biochemical Journal · doi:10.1042/bj3180805 · Cited by 74 · see citing works
Decreased production of reactive oxygen intermediates is an early event during in vitro apoptosis of rat thymocytes
Wang, J., Jerrells, T. R., & Spitzer, J. J. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)02085-3 · Cited by 75 · see citing works
Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications
Kamiński, M. M., Röth, D., Krammer, P. H., & Gülow, K. (2013) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-013-0235-0 · Cited by 72 · see citing works
Hydrogen peroxide is involved in lymphocyte activation mechanisms to induce angiogenesis
Monte, M., Davel, L., & de Lustig, E. S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00506-0 · Cited by 71 · see citing works
Preterm premature rupture of the membranes and antioxidants: the free radical connection
Wall, P. D., Pressman, E. K., & Woods, J. R. (2002) · Journal of Perinatal Medicine · doi:10.1515/jpm.2002.071 · Cited by 68 · see citing works
Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model
Jayle, C., Favreau, F. D., Zhang, K., et al. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00338.2006 · Cited by 65 · see citing works
Inhibition of murine T-cell responses by anti-oxidants: the targets of lipo-oxygenase pathway inhibitors.
Dornand, J., & Gerber, M. (1989) · PubMed · Cited by 62 · see citing works
Riboflavin-Mediated Reduction of Oxidant Injury, Rejection, and Vasculopathy after Cardiac Allotransplantation
Iwanaga, K., Hasegawa, T., Hultquist, D. E., et al. (2007) · Transplantation · doi:10.1097/01.tp.0000256283.06469.d4 · Cited by 61 · see citing works
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Background
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Self-citation
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Renton, F. J., & Jeitner, T. M. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00099-8 · Cited by 57 · see citing works
Transcription factors as targets for oxidative signalling during lymphocyte activation
Goldstone, S. D., Fragonas, J., Jeitner, T. M., et al. (1995) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(95)00088-x · Cited by 57 · see citing works
Self-citation
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Laniewski, N. G., & Grayson, J. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.20.11246-11257.2004 · Cited by 55 · see citing works
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Result
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Thumwood, C. M., Hunt, N. H., Cowden, W. B., & Clark, I. A. (1989) · PubMed Central · Cited by 56 · see citing works
Self-citation
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Simeoni, L., & Bogeski, I. (2015) · Biological Chemistry · doi:10.1515/hsz-2014-0312 · Cited by 52 · see citing works
In vitro antioxidant treatment recovers proliferative responses of anergic CD4+ lymphocytes from human immunodeficiency virus-infected individuals
Cayota, A., Vuillier, F., Gonzalez, G. A., & Dighiero, G. (1996) · Blood · doi:10.1182/blood.v87.11.4746.bloodjournal87114746 · Cited by 49 · see citing works
Review Article the B Lymphocyte: A Newly Recognized Source of Reactive Oxygen Species with Immunoregulatory Potential
Maly, F. E. (1990) · Free Radical Research Communications · doi:10.3109/10715769009087987 · Cited by 46 · see citing works
The intracellular oxidation of 2′,7′-dichlorofluorescin in murine T lymphocytes
van Reyk, D. M., King, N. J. C., Dinauer, M. C., & Hunt, N. H. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00449-4 · Cited by 45 · see citing works
Self-citation
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Patsoukis, N., Bardhan, K., Weaver, J. D., Herbel, C., Seth, P., Li, L., & Boussiotis, V. A. (2016) · PubMed · Cited by 41 · see citing works
Melatonin in vivo prolongs cardiac allograft survival in rats
Jung, F. J., Yang, L., Härter, L., et al. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00133.x · Cited by 42 · see citing works
“Antioxidants and hydroxyl radical scavengers have been used to inhibit T cell proliferation and IL-2 receptor expression on stimulated T cells in vitro [24, 25].”
Background
No Life Without Death
Krammer, P. H., Kamiński, M. M., Kießling, M. K., & Gülow, K. (2007) · Advances in cancer research · doi:10.1016/s0065-230x(06)97005-5 · Cited by 42 · see citing works
Age-dependent modifications of mitochondrial trans-membrane potential and mass in rat splenic lymphocytes during proliferation
Pieri, C., Recchioni, R., & Moroni, F. (1993) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(93)90048-v · Cited by 39 · see citing works
Increased oxidative metabolism in PMA-activated lymphocytes: A flow cytometric study
Rabesandratana, H., Fournier, A.-M., Château, M., et al. (1992) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(92)90089-4 · Cited by 39 · see citing works
Carnosine (beta-alanylhistidine) protects from the suppression of contact hypersensitivity by ultraviolet B (280-320 nm) radiation or by cis urocanic acid.
Reeve, V. E., Bosnic, M., & Rozinova, E. (1993) · PubMed · Cited by 39 · see citing works
Expression of Pgp‐1 (or Ly24) by subpopulations of mouse thymocytes and activated peripheral T lymphocytes
Lynch, F., Chaudhri, G., Allan, J. E., et al. (1987) · European Journal of Immunology · doi:10.1002/eji.1830170123 · Cited by 37 · see citing works
Self-citation
Development of the “activated” high resolution 1H MR spectrum in murine T cells and B cells occurs in G1 phase of the cell cycle
Holmes, K. T., Lean, C. L., Hunt, N. H., & King, N. J. C. (1990) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910160102 · Cited by 36 · see citing works
Self-citation
INHIBITION OF FREE RADICAL GENERATION AND IMPROVED SURVIVAL BY PROTECTION OF THE HEPATIC MICROVASCULAR ENDOTHELIUM BY TARGETED ERYTHROCYTES IN ORTHOTOPIC RAT LIVER TRANSPLANTATION
Rao, P. N., Walsh, T. R., Makowka, L., et al. (1990) · Transplantation · doi:10.1097/00007890-199006000-00006 · Cited by 33 · see citing works
Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine.
Polson, R. J., Jenkins, R., Lombard, M. C., et al. (1990) · PubMed · Cited by 33 · see citing works
Mechanisms regulating immune surveillance of cellular stress in cancer
Seelige, R., Searles, S. C., & Bui, J. D. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2597-7 · Cited by 31 · see citing works
“In line with that, antioxidants directly inhibit T-cell activation, proliferation and IL-2 receptor expression [24, 25, 123].”
Background
Oxidative signalling and gene expression during lymphocyte activation
Goldstone, S. D., Milligan, A., & Hunt, N. H. (1996) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(96)00082-1 · Cited by 31 · see citing works
Self-citation
Differential effects of the antioxidant α-lipoic acid on the proliferation of mitogen-stimulated peripheral blood lymphocytes and leukaemic T cells
Pack, R. A., Hardy, K., Madigan, M. C., & Hunt, N. H. (2002) · Molecular Immunology · doi:10.1016/s0161-5890(01)00110-9 · Cited by 30 · see citing works
Self-citation
Amelioration of murine cerebral malaria by dietary restriction
Hunt, N. H., Manduci, N., & Thumwood, C. M. (1993) · Parasitology · doi:10.1017/s0031182000068049 · Cited by 29 · see citing works
Self-citation
Artesunate and artelinic acid: association of embryotoxicity, reticulocytopenia, and delayed stimulation of hematopoiesis in pregnant rats.
Clark, R., Brannen, K., Sanders, J. E., & Hoberman, A. (2011) · Birth defects research. Part B. Developmental and reproductice toxicology · doi:10.1002/bdrb.20282 · Cited by 27 · see citing works
In vivo immunoregulatory properties of the novel mitochondria-targeted antioxidant SkQ1
Yang, Y., Karakhanova, S., Soltek, S., Werner, J., Philippov, P. P., & Bazhin, A. V. (2012) · Molecular Immunology · doi:10.1016/j.molimm.2012.04.010 · Cited by 27 · see citing works
Role of oxidant injury on macrophage lipoprotein lipase (LPL) production and sensitivity to LPL
Renier, G., Desfaits, A.-C., Lambert, A., et al. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37578-7 · Cited by 27 · see citing works
Interference with oxidative processes inhibits proliferation of human peripheral blood lymphocytes and murine B-lymphocytes
Hunt, N. H., Cook, E. P., & Fragonas, J. (1991) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(91)90056-d · Cited by 26 · see citing works
Self-citation
The nexus between redox state and intermediary metabolism
Zoccarato, A., Nabeebaccus, A., Oexner, R. R., Santos, C. X. C., & Shah, A. M. (2021) · FEBS Journal · doi:10.1111/febs.16191 · Cited by 27 · see citing works
Appraisal of Potential Therapeutic Index of Antioxidants on the Basis of Their In Vitro Effects on HIV Replication in Monocytes and Interleukin 2-Induced Lymphocyte Proliferation
Aillet, F., Gougerot‐Pocidalo, M., Virelizier, J., et al. (1994) · AIDS Research and Human Retroviruses · doi:10.1089/aid.1994.10.405 · Cited by 25 · see citing works
Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia–reperfusion injury
Sullivan, P. J., Sweeney, K. J., Hirpara, K. M., et al. (2009) · British journal of surgery · doi:10.1002/bjs.6554 · Cited by 23 · see citing works
Inhibition of allergic encephalomyelitis by the iron chelating agent desferrioxamine: differential effect depending on type of sensitizing encephalitogen
Willenborg, D. O., Bowern, N. A., Danta, G., & Doherty, P. C. (1988) · Journal of Neuroimmunology · doi:10.1016/0165-5728(88)90020-3 · Cited by 23 · see citing works
Reactive oxygen species and not lipoxygenase products are required for mouse B-lymphocyte activation and differentiation
Fedyk, E. R., & Phipps, R. P. (1994) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(94)90105-8 · Cited by 23 · see citing works
Superoxide generation by EBV-transformed B lymphocytes. Activation by IL-1 beta, TNF-alpha and receptor independent stimuli.
Hancock, J. T., HENDERSON, L. M., & Jones, O. (1990) · PubMed · Cited by 23 · see citing works
Effects of anti-oxidants on ornithine decar☐ylase in mitogenically-activated T lymphocytes
Hunt, N. H., & Fragonas, J. (1992) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(92)90046-e · Cited by 22 · see citing works
Self-citation
T‐Cell Chemiluminescence
Bénichou, G., Kanellopoulos, J., Mitenne, F., et al. (1989) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1989.tb01210.x · Cited by 21 · see citing works
Increased Cell Surface Free Thiols Identify Effector CD8+ T Cells Undergoing T Cell Receptor Stimulation
Pellom, S. T., Michalek, R. D., Crump, K. E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081134 · Cited by 19 · see citing works
“This increase is essential for activation as antioxidant treatment, which lowers ROI, decreases T cell activation [4].”
Background
Oxidative stress and coxsackievirus infections as mediators of beta cell damage: a review.
Sharma, V., Kalim, S., Srivastava, M. K., Nanda, S., & Mishra, S. (2009) · Scientific Research and Essays · doi:10.5897/sre.9000707 · Cited by 18 · see citing works
Peroxiredoxin II Regulates Effector and Secondary Memory CD8<sup>+</sup>T Cell Responses
Michalek, R. D., Crump, K. E., Weant, A. E., Hiltbold, E. M., Juneau, D. G., Moon, E.-Y., Yu, D.-Y., Poole, L. B., & Grayson, J. M. (2012) · Journal of Virology · doi:10.1128/jvi.01559-12 · Cited by 17 · see citing works
“These changes are critical because antioxidant treatment, which lowers ROI, decreases activation and proliferation (9).”
Background
ROS-Responsive Biomaterial Design for Medical Applications
Lee, J. B., Shin, Y. M., Kim, W. S., Kim, S. Y., & Sung, H. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0445-3_15 · Cited by 18 · see citing works
Effects of training on spleen and peritoneal exudate reactive oxygen species and lymphocyte proliferation by splenocytes at rest and after an acute bout of exercise
Kwak, Y. (2006) · Journal of Sports Sciences · doi:10.1080/02640410500386233 · Cited by 17 · see citing works
Oxygen radical production by transformed B lymphocytes
Jones, O., Hancock, J. T., & HENDERSON, L. M. (1991) · Molecular Aspects of Medicine · doi:10.1016/0098-2997(91)90004-6 · Cited by 17 · see citing works
Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus
Benke, P. J., Levcovitz, H., Paupe, J., & Tozman, E. (1990) · Metabolism · doi:10.1016/0026-0495(90)90184-e · Cited by 17 · see citing works
Inhibition of in vitro lymphoproliferation by three novel iron chelators of the pyridoxal and salicyl aldehyde hydrazone classes
van Reyk, D. M., Sarel, S., & Hunt, N. H. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00347-6 · Cited by 16 · see citing works
Self-citation
In vitro effects of three iron chelators on mitogen-activated lymphocytes: Identification of differences in their mechanisms of action
van Reyk, D. M., Sarel, S., & Hunt, N. H. (1992) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(92)90092-y · Cited by 16 · see citing works
Self-citation
Effect of orally active hydroxypyridinone iron chelators on human lymphocyte function
Pattanapanyasat, K., Webster, H. K., Tongtawe, P., et al. (1992) · British Journal of Haematology · doi:10.1111/j.1365-2141.1992.tb04587.x · Cited by 16 · see citing works
“This differs from previous work showing that DF inhibited the process of T-cell activation either by directly inhibiting expression of IL-2 receptors (Carotenuto et al, 1986) or by suppressing the generation of hydroxyl radical formation essential to IL-2 receptor expression (Chaudhri et al. 1986).”
Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine
Nottet, H. S. L. M., van Asbeck, B. S., de Graaf, L., Vos, N., Visser, M. R., & Verhoef, J. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.56.6.702 · Cited by 15 · see citing works
“Hydroxyl radicals reduce the activity of membraneassociated tumor necrosis factor a (TNF-a) receptors on monocytes [37, 38] and induce the expression of interleukin-2 (IL-2) receptors on stimulated T cells [39].”
Background
Physiological Functions of Mitochondrial Reactive Oxygen Species
Choi, T. G., & Kim, S. S. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88386 · Cited by 15 · see citing works
Redox Mechanisms in T Cell Activation
Hunt, N. H., van Reyk, D. M., Fragonas, J., et al. (1994) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-7424-3_21 · Cited by 14 · see citing works
Self-citation
The Protective Role of 1,8-Dihydroxynaphthalene–Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides
Keizer, E., Valdes, I. D., McCann, B. L., Bignell, E., Wösten, H. A. B., & de Cock, H. (2022) · mSphere · doi:10.1128/msphere.00874-21 · Cited by 12 · see citing works
Carbon Monoxide Inhibits T Cell Proliferation by Suppressing Reactive Oxygen Species Signaling
Yan, Y., Wang, L., Chen, S., Zhao, G., Fu, C., Xu, B., Tan, X., Xiang, Y., & Chen, G. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7814 · Cited by 13 · see citing works
“Furthermore, preventing intra-cellular ROS generation with antioxidants or by using T-Uqcrfs -/- mice with reduced mitochondrial ROS production in their T cells can signiﬁcantly inhibit antigen-speciﬁc T cell activation and proliferation (8,46).”
Intracellular Cu/Zn superoxide dismutase levels in T and non-T cells from normal aged subjects
Grigolo, B., Borzı̀, R. M., Mariani, E., Monaco, M., Cattini, L., Porstmann, T., & Facchini, A. (1994) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(94)90035-3 · Cited by 12 · see citing works

Authors: Chaudhri, G., Clark, I. A., Hunt, N. H., Cowden, W. B., & Ceredig, R.
Affiliations: Australian National University (AU)
ORCID: Chaudhri, G
Hunt, N H
Ceredig, R
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 1986-10
Volume: 137
Issue: 8
Pages: 2646-2652
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.137.8.2646
OpenAlex: W1563909789
Cited by: 138
References: 0
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2022: 3 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 4
FWCI: 1.69
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: antioxidants, oxygen free radicals, T cell activation, alloantigen, lymphocyte proliferation, mixed lymphocyte reaction, ferricyanide, iron chelators, deferoxamine, pyridoxal isonicotinoyl hydrazone, butylated hydroxyanisole, interleukin-2 receptor, interleukin-1, interleukin-2, cell-mediated immunity
MeSH terms: Animals, Antioxidants, Female, Flow Cytometry, Interleukin-2, Isoantigens, Kinetics, Lymphocyte Culture Test, Mixed, Lymphocyte Activation, Mice, Inbred CBA, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, T-Lymphocytes, Mice

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Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation

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