Summary
A variety of anti-oxidants, including free radical scavengers and iron chelators, inhibit the proliferation of mitogenstimulated T lymphocytes in vitro. These agents do not operate by inhibiting the induction of omithine decarboxylase activity. Phorbol myristate acetate induces formation of reactive oxygen species in T cell-enriched populations. Flow cytometry has identified this reactive oxygen within the T lymphocytes themselves, though other cells may contribute indirectly. The binding to DNA of the transcription factors AP-1 and NF-kB is increased during the commitment period, 2–4 hours after mitogen addition to T lymphocytes, and this binding is inhibited by the anti-oxidant aminothiol compound, cysteamine. Intracellular oxidant formation in mitogen-stimulated T cells might activate transcription factors, allowing their translocation into the nucleus and subsequent reduction and binding to DNA, thereby inducing early gene expression. Since the replication of the human immunodeficiency virus-1 is linked to NF-kB and can be inhibited by some anti-oxidants, it is possible that this virus is stimulated to replicate by the intracellular oxidative events that we have shown to be an obligatory step in T lymphocyte recruitment into the cell cycle.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bannister, A.J., Cook, A., and Kouzarides, T. (1991) In vitro DNA binding activity of Fos/Jun and BZLF1 but not C/EBP is affected by redox changes. Oncogene 6: 1243–1250.
Bass, D.A., Parce, J.W., Dechatelet, L.R., Szedja, P., Seeds, M.C., and Thomas, M. (1983) Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J. Immunol. 130: 1910–1917.
Bierer, B.E., and Nathan, D.G. (1990) The effect of desferrithiocin, an oral iron chelator, on T-cell function. Blood 76: 2052–2059.
Blatt, J., Taylor, S.R., and Kontoghiorghes, G.J. (1989) Comparison of activity of deferoxamine with that of oral iron chelators against human neuroblastoma cell lines. Cancer Res. 49: 2925–2927.
Carotenuto, P., Pontesilli, O., Cambier, J.C., and Hayward, A.R. (1986) Desferoxamine blocks IL 2 receptor expression on human T lymphocytes. J. Immunol. 136: 2342–2347.
Carter, R., Cosenza, S.C., Pena, A., Lipson, K., Soprano, D.R., and Soprano, K.J. (1991) A potential role for c-jun in cell cycle progression through late G t and S. Oncogene 6: 229–235.
Celano, P., Baylin, S.B., and Casero, R.A.,Jr. (1989) Polyamines differentially modulate the trnscription of growth-associated genes in human colon carcinoma cells. J. Biol. Chem. 264: 8922–8927.
Chaudhri, G., Clark, I.A., Hunt, N.H., Cowden, W.B., and Ceredig, R. (1986) Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. J. Immunol. 137: 2646–2652.
Chaudhri, G., Hunt, N.H., Clark, I.A., and Ceredig, R.H. (1988) Antioxidants inhibit proliferation and cell surface expression of receptors for interleukin 2 and transferrin in T lymphocytes stimulated with PMA and ionomycin. Cell. Immunol. 115: 204–213.
Chinnadurai, G. (1991) Modulation of HIV-enhancer activity by heterologous agents: A minireview. Gene 101: 165–170.
Darley-Usmar, V.M., Hersey, A., and Garland, L.G. (1989) A method for the comparative assessment of antioxidants as peroxyl radical scavengers. Biochem. Pharmacol. 38: 1465–1469.
Dornand, J. and Gerber, M. (1989) Inhibition of murine T-cell responses by anti-oxidants: The targets of lipo-oxygenase pathway inhibitors. Immunology 68: 384–391.
Dröge, W., Eck, H.-P., Näher, H., Pekar, U., and Daniel, V. (1988) Abnormal amino-acid concentrations in the blood of patients with acquired immunodeficiency syndrome (AIDS) may contribute to the immunological defect. Biol. Chem. Hoppe-Seyler 369: 143–148.
Estrov, Z., Tawa, A., Wang, X-H., Dubé, I.D., Sulh, H., Cohen, A., Gelfand, E.W., and Freedman, M.H. (1987) In vitro and in vivo effects of deferoxamine in neonatal acute leukemia. Blood 69: 757–761.
Fidelus, R.K. and Tsan, M.-F. (1986) Enhancement of intracellular glutathione promotes lymphocyte activation by mitogen. Cell. Immunol. 97: 155–163.
Fidelus, R.K. (1988) The generation of oxygen radicals: a positive signal for lymphocyte activation. Cell. Immunol. 113: 175–182.
Ganeshaguru, K., Hoffbrand, A.V., Grady, R.W., and Cerami, A. (1980) Effect of various iron chelating agents on DNA synthesis in human cells. Biochem. Pharmacol. 29: 1275–1279.
Granelli-Piperno, A. and Nolan, P. (1991) Nuclear transcription factors that bind to elements of the IL-2 promoter: Induction requirements in primary human T cells. J. Immunl. 147: 2734–2739.
Halliwell, B. and Gutteridge, J.M.C. (1989) Free radicals in biology and medicine, Oxford, Clarendon Press.
Hamilos, D.L., Zelarney, P., and Mascali, J.J. (1989) Lymphocyte proliferation in glutathionedepleted lymphocytes: Direct relationship between glutathione availability and the proliferative response. Immunopharmacology 18: 223–235.
Harakeh, S. and Jariwalla, R.J. (1991) Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells. Am. J. Clin. Nutr. 54 Suppl.: 1231S - 1235S.
Hoffbrand, A.V., Ganeshaguru, K., Hooton, J.W.L., and Tattersall, M.N.H. (1976) Effect of iron deficiency and desferrioxamine on DNA synthesis in human cells. Br. J. Haematol. 33: 515–552.
Hunt, N.H., Chaudhri, G., Buffinton, G.D., Cook, E., Cowden, W.B., Clark, I.A., and Dorsch, S.E. (1989) Iron and infectious disease. In: Free Radicals, Metal Ions and Biopolymers, 233247. Edited by Beaumont, P., Deeble, D., Parsons, B., and Rice-Evans, C., London, Richelieu Press.
Hunt, N.H., Cook, E.P., and Fragonas, J.-C. (1991) Interference with oxidative processes inhibits proliferation of human peripheral blood lymphocytes and murine B-lymphocytes. Int. J. Immunopharmacol. 13: 1019–1026.
Hunt, N.H. and Fragonas, J.-C. (1992) Effects of anti-oxidants on ornithine decarboxylase in mitogenically-activated T lymphocytes. Biochim. Biophys. Acta 1133: 261–267.
Hunt, N.H., Fragonas, J.-C., Kneale, C.L., Jeitner, T.M., and Van Reyk, D.M. (1992) Antioxidants and T cell activation. In: Active Oxygens, Lipid Peroxides and Antioxidants, 719–722. Edited by Yagi, K., Kondo, M., Niki, E., and Yoshikawa, T., Amsterdam, Elsevier Excerpta Medica.
Hwang, C., Sinskey, A.J., and Lodish, H.F. (1992) Oxidized redox state of glutathione in the endoplasmic reticulum. Science 257: 1496–1502.
Israel, N., Gougerot-Pocidalo, M.-A., Aillet, F., and Virelizier, J.L. (1992) Redox status of cells influences constitutive or induced NF-kB translocation and HIV long terminal repeat activity in human T and monocytic cell lines. J. Immunol. 149: 3386–3393.
Jeitner, T.M. and Hunt, N.H. (1990) Cysteamine and its phenolic analogues inhibit the proliferation of normal, leukemic and drug resistant leukemic T cells. Free Radic. Biol. Med. 9: 172.
Jeitner, T.M. and Oliver, J.R. (1990) Possible oncostatic action of cysteamine on the pituitary glands of oestrogen-primed hyperprolactinaemic rats. J. Endocrinol. 127: 119–127.
Kalebic, T., Kinter, A., Poli, G., Anderson, M.E., Meister, A., and Fauci, A.S. (1991) Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. Proc. Natl. Acad. Sci. USA 88: 986–990.
Kolbuch-Braddon, M.E., Peterhans, E., Stocker, R., and Weidemann, M.J. (1984) Oxygen uptake associated with Sendai-virus-stimulated chemiluminescence in rat thymocytes contains a significant non-mitochondrial component. Biochem. J. 222: 541–551.
Lacal, P.M., Balsinde, J., Cabanas, C., Bernabeu, C., Sanchez-Madrid, F., and Mollinedo, F. (1990) The CD! is antigen couples concanavalin A binding to generation of superoxide anion in human phagocytes. Biochem. J. 268: 707–712.
Lederman, H.M., Cohen, A., Lee, J.W.W., Freedman, M.H., and Gelfand, E.W. (1984) Blood 64: 748–753.
Lenardo, M.J. and Baltimore, D. (1989) NF-kB: a pleiotropic mediator of inducible and tissue-specific gene control. Cell 58: 227–229.
Maly, F.-E., Nakamura, M., Gauchat, J.-F., Urwyler, A., Walker, C., Dahinden, C.A., Cross, A.R., Jones, O.T.G., and De Weck, A.L. (1989) Superoxide-dependent nitroblue tetrazolium reduction and expression of cytochrome b-245 components by human tonsillar B lymphocytes and B cell lines. J. Immunl. 142: 1260–1267.
Novogrodsky, A., Ravid, A., Rubin, A.L., and Stenzel, K.H. (1982) Hydroxyl radical scavengers inhibit lymphocyte mitogenesis. Proc. Natl. Acad. Sci. USA 79: 1171–1174.
Parnham, M.J. and Graf, E. (1987) Seleno-organic compounds and the therapy of hydroperoxide-linked pathological conditions. Biochem. Pharmacol. 36: 3095–3102.
Pardee, A.B. (1989) GI events and regulation of cell proliferation. Science 246: 603–608.
Peterhans, E., Jungi, T.W., and Stocker, R.S. (1989) Autotoxicity and reactive oxygen in viral disease. In: Oxy-Radicals in Molecular Biology and Pathology, 543–562. Edited by Cerutti, P.A., Fridovich, I., and McCord, J.M., New York, Alan R. Liss.
Pick, E. and Gadba, R. (1988) Certain lymphoid cells contain the membrane-associated component of the phagocyte-specific NADPH oxidase. J. Immunol. 140: 1611–1617.
Pollack, S., Aisen, P., Lasky, F.D., and Vanderhoff, G. (1976) Chelate mediated transfer of iron from transferrin to desferrioxamine. Brit. J. Haematol. 34: 231–235.
Poison, R.J., Jenkins, R., Lombard, M., Williams, A.C., Roberts, S., Nouri-Aria, K., Williams, R., and Bomford, A. (1990) Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine. Immunology 71: 176–181.
Rabesandratana, H., Fournier, A.-M., Chateau, M.-T., Serre, A., and Dornand, J. (1992) Increased oxidative metabolism in PMA-activated lymphocytes: a flow cytometric study. Int. J. Immunopharmacol. 14: 895–902.
Roederer, M., Staal, F.J.T., Raju, P.A., Ela, W.S., and Herzenberg, L.A. (1990) Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc. Natl. Acad. Sci. USA 87: 4884–4888.
Sagone, A.L.,Jr., Husney, R., Guter, H., and Clark, L. (1984) Effect of catalase on the proliferation of human lymphocytes to phorbol myristate acetate. J. Immunol. 133: 1488–1494.
Schreck, R., Meier, B., Mannel, D.N., Droge, W., and Baeuerle, P.A. (1992) Dithiocarbamates as potent inhibitors of nuclear factor kB activation in intact cells. J. Exp. Med. 175: 1181–1194.
Schreck, R., Rieber, P., and Baeuerle, P.A. (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kB transcription factor and HIV-1. EMBO J. 10: 2247–2258.
Sekkat, C., Dornand, J., and Gerber, M. (1988) Oxidative phenomena are implicated in human T-cell stimulation. Immunology 63: 431–437.
Smit, M.J. and Anderson, R. (1990) Inhibition of mitogen-activated proliferation of human lymphocytes by hypochlorous acid in vitro: Protection and reversal by ascorbate and cysteine. Agents and Actions 30: 338–343.
Staal, F.J.T., Roederer, M., Herzenberg, L.A., and Herzenberg, L.X. (1990) Intracellular thiols regulate activation of nuclear factor kB and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. (USA) 87: 9943–9947.
Suthanthiran, M., Anderson, M.E., Sharma, V.K., and Meister, A. (1990) Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc. Natl. Acad. Sci. USA 87: 3343–3347.
Terada, N., Or, R., Szepesi, A., Lucas, J.J., and Gelfand, E.W. (1993) Definition of the roles for iron and essential fatty acids in cell cycle progression of normal human T lymphocytes. Exp. Cell Res. 204: 260–267.
Ullman, K.S., Northrop, J.P., Verweij, C.L., and Crabtree, G.R. (1990) Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: The missing link. Annu. Rev. Immunol. 8 421–452.
Unanue, E.R. (1992) Cellular studies on antigen presentation by class II MHC molecules. Curr. Opinion Immunl. 4: 63–69.
van Reyk, D.M., Sarei, S., and Hunt, N.H. (1992) Inhibition of lymphocyte proliferation by three putative iron chelators: Identification of differences in their mechanisms of action. Int. J. Immunopharmacol. 14: 925–932.
Weidemann, M.J., Yin Foo, D., Kolbuch-Braddon, M.E., Mitchell, S.V., Domzig, W., and Peterhans, E. (1987) Characterisation of chemiluminescence-generating subpopulations within the rodent thymus. In: Proceedings of the Fourth International Bioluminescence Symposium, 109–112. Edited by Schoelmerich, J., New York, Wiley.
White, M.W., Kameji, T., Pegg, A.E., and Morris, D.R. (1987) Increased efficiency of translation of ornithine decarboxylase mRNA in mitogen-activated lymphocytes. Eur. J. Biochem. 170: 87–92.
Wrogemann, K., Weidemann, M.J., Peskar, B.A., Staudinger, H., Rietschel, E.T., and Fischer, H. (1978) Chemiluminescence and immune activation. 1. Early activation of rat thymocytes can be monitored by chemiluminescence measurements. Eur. J. Immunl. 8: 749–752.
Xanthoudakis, S., Miao, G., Wang, F., Pan, Y.-C.E., and Curran, T. (1992) Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. Embo J. 11: 3323–3335.
Yudkoff, M., Foreman, J.W. and Segal, S. (1981) Effects of cysteamine therapy in nephropathic cystinosis. N. Engl. J. Med. 304: 141–145.
Yuhas, J.M. (1980) On the potential application of radioprotective drugs in solid tumor radiotherapy. In: Radiation-Drug Interactions in the TReatment of Cancer, 113–134. Edited by Sokol, G.H. and Maickel, R.P., New York, Wiley.
Zoschke, D.C. and Staite, N.D. (1987) Suppression of human lymphocyte proliferation by activated neutrophils or H2O2: surviving cells have an altered T helper/T suppressor ratio and an increased resistance to secondary oxidant exposure. Clin. Immunol. Immunopathol. 42: 160–170.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Hunt, N.H., van Reyk, D.M., Fragonas, J.C., Jeitner, T.M., Goldstone, S.D. (1994). Redox Mechanisms in T Cell Activation. In: Pasquier, C., Olivier, R.Y., Auclair, C., Packer, L. (eds) Oxidative Stress, Cell Activation and Viral Infection. Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7424-3_21
Download citation
DOI: https://doi.org/10.1007/978-3-0348-7424-3_21
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-0348-7426-7
Online ISBN: 978-3-0348-7424-3
eBook Packages: Springer Book Archive