Reactive oxygen species selectively deplete normal T lymphocytes via a hydroxyl radical dependent mechanism.
Chronic inflammatory synovitis is characterized by both lymphocytic infiltrates and persistent polymorph exudates. Activated polymorphs release reactive oxygen species (ROS) during inflammation, but the contribution that these make to the lymphocyte abnormalities associated with RA has been little studied. We therefore investigated the cytotoxic effects of the reactive oxygen species on human peripheral blood mononuclear cells (PBMC). PBMC were exposed to RPMI 1640 medium previously irradiated for up to 60 min. Consistent dose-dependent killing was observed at 24 h. Antioxidant studies indicated that H2O2 was the effective species. Catalase, which specifically degrades H2O2, gave almost total protection against cell death, while superoxide dismutase (SOD), thiourea, and mannitol were largely ineffective. Addition of exogenous H2O2 caused an identical pattern of cell death to that observed with irradiated medium. PBMC cultures supplemented with desferrioxamine (a ferric iron chelator) also gave significant protection, suggesting that H2O2 mediated its effects via OH radicals. Analysis of lymphocyte subpopulations showed that ROS caused a selective depletion, depending on the level of H2O2 present. Low levels induced a specific loss of CD8+ cells, while higher concentrations caused significant loss of CD4+ T cells as well. sIg+ B cells were unaffected at either concentration. This selective lymphotoxic effect of ROS may be of considerable importance in the pathogenesis of autoimmune inflammatory disease.
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000528:radiation effects; D003676:Deferoxamine / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D006878:Hydroxides; D017665:Hydroxyl Radical; D013585:Synovitis / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects
D000975:Antioxidants; D006878:Hydroxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D003676:Deferoxamine