Abstract
The use of antioxidant compounds with differing modes of action has clearly demonstrated involvement of oxidative processes in the activation of T lymphocytes.-In this paper, we show that a novel antioxidant (lazaroid U75412E, a free radical scavenger) suppressed mitogen-induced T cell proliferationin vitro. Similar results were obtained with diphenylene iodonium (DPI), a known inhibitor of NADPH oxidase. The lazaroid was further shown to inhibit IL 2 production but to be less potent in suppressing IL 2 receptor expression. Thus, scavenger-type antioxidants act on T cells primarily by blocking a signal necessary for the induction of IL 2 synthesis such as the activation of NFκB. Furthermore, the potent inhibition of lymphocyte responses caused by the specific enzyme inhibitor DPI provides direct proof of the source of the oxidants involved in these processes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
A. Novogrodsky, A. Ravid, A. L. Rubin and K. H. Stenzel,Hydroxyl radical scavengers inhibit lymphocyte mitogenesis. Proc. Natl. Acad. Sci. USA79, 1171–1174 (1982).
G. Chaudri, I. A. Clark, N. H. Hunt, W. B. Cowden and R. Ceredig,Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. J. Immunol.137, 2646–2652 (1986).
J. Dornand and M. Gerber,Inhibition of murine T-cell responses by antioxidants: The targets of lipo-oxygenase pathway inhibitors. Immunology68, 384–391 (1989).
A. Finazzi-Agro, P. Conti, M. Hofmann, P. U. Angeletti and G. Rotilio,Activation of lymphocytes by H 2 O 2 Agents and Actions (Suppl.)7, 220–223 (1980).
R. Schreck, P. Rieber and P. A. Baeuerle,Reactive oxygen intermediates as apparently widely used messengers in the activation of the NFκB transcription factor and HIV-1. EMBO J.10, 2247–2258 (1991).
J. M. Braughler, J. F. Pregenzer, R. L. Chase, L. A. Duncan, E. J. Jacobsen and J. M. McCall,Novel 21-amino steroids as potent inhibitors of iron-dependent lipid peroxidation. J. Biol. Chem.262, 10438–10440 (1987).
A. R. Cross and O. T. G. Jones,The effect of the inhibitor diphenylene iodonium on the superoxide-generating system of neutrophils. Biochem. J.237, 111–116 (1986).
I. Ando and P. C. L. Beverley,A simple microassay for interleukin-2 activity. J Immunol. Meth.96, 133–137 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kalsi, J.K., Clay, K., Rickard, D. et al. Suppressive effects of a novel antioxidant compound on human T cell functionsin vitro . Agents and Actions 39 (Suppl 1), C110–C112 (1993). https://doi.org/10.1007/BF01972738
Issue Date:
DOI: https://doi.org/10.1007/BF01972738