Inhibition of Early Events in the Human T-Lymphocyte Response to Mitogens and Alloantigens by Hydrogen Peroxide

• 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)