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Inhibition of Early Events in the Human T-Lymphocyte Response to Mitogens and Alloantigens by Hydrogen Peroxide
Brian M. Freed, MA;
Robert Rapoport;
Neil Lempert, MD
Arch Surg. 1987;122(1):99-104.
Abstract
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Hydrogen peroxide (100 to 200µM) inhibited the response of human peripheral-blood mononuclear cells (PBMCs) in phytohemagglutinin, concanavalin A, and mixed lymphocyte culture assays by more than 90% without affecting cell viability. The response of PBMCs to pokeweed mitogen was stimulated twofold by 50µM H2O2, but 200µM H2O2 inhibited the pokeweed mitogen response by more than 95%. A 50µM concentration of H2O2 completely blocked the generation of cytotoxic T cells in the mixed lymphocyte culture but did not inhibit the production of interleukin 2. Concentrations of 100µM to 200µM H2O2 inhibited interleukin 2 production by 45% to 57%. The H2O2 appeared to block early events in T-cell activation, since 200µM H2O2 was not inhibitory when added one hour after stimulating the cells with phytohemagglutinin. Treatment of PBMCs with 200µM H2O2 did not decrease the total cellular thiol pool, suggesting that H2O2-mediated inhibition of the proliferative response was not due to thiol oxidation. However, pretreatment of PBMCs with the lipid antioxidants butylated hydroxyanisole, butylated hydroxytoluene, and n-propyl gallate blocked more than 75% of the inhibitory effect of H2O2, suggesting that H2O2 inhibits T-cell activation by inducing lipid peroxidation.
(Arch Surg 1987;122:99-104)
Author Affiliations
From the Transplantation Immunology Laboratory, Department of Surgery, Albany (NY) Medical College of Union University.
Footnotes
Accepted for publication Aug 11, 1986.
Read before the Sixth Annual Meeting of the Surgical Infection Society, Chicago, April 22, 1986.
Reprint requests to Transplantation Immunology Laboratory, Department of Surgery, Albany Medical College of Union University, Albany, NY 12208 (Dr Lempert).
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