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.
Either activated neutrophils (PMNs) or nanomole amounts of reagent hydrogen peroxide (H2O2) were found to cause catalase-reversible suppression of concanavalin A (Con A)-stimulated human lymphocyte proliferation. Suppression required PMN activation and occurred with PMN/lymphocyte ratios found in peripheral blood. Inhibition by reagent H2O2 occurred with 10-40 nmol H2O2/1 X 10(6) lymphocytes, a noncytolethal amount which is produced readily by PMA-activated PMNs. Lymphoblasts recovered from suppressed cultures were two- to fourfold less sensitive than control lymphoblasts to a second exposure to H2O2. These relatively H2O2-resistant lymphoblasts also scavenge H2O2 at higher rates than do control lymphoblasts. Progeny lymphocytes from suppressed cultures contain an unusually high percentage of T helper cells with a concomitant decrease in T suppressors. These studies demonstrate a potential immunoregulatory role for phagocyte-released oxidants, especially H2O2, and suggest a possible additional mechanism to explain the excess of T helpers observed in situations of chronic inflammation.
D000954:Antigens, Surface; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003864:Depression, Chemical; D004351:Drug Resistance; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000954:Antigens, Surface; D003208:Concanavalin A; D006861:Hydrogen Peroxide; D002374:Catalase; D013755:Tetradecanoylphorbol Acetate