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Reactive Oxygen Species Selectively Deplete Normal T Lymphocytes Via a Hydroxyl Radical Dependent Mechanism
Author(s) -
ALLAN I. M.,
LUNEC J.,
SALMON M.,
BACON P. A.
Publication year - 1987
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1987.tb02233.x
Subject(s) - reactive oxygen species , catalase , superoxide dismutase , chemistry , peripheral blood mononuclear cell , hydroxyl radical , superoxide , lymphocyte , oxidative stress , microbiology and biotechnology , antioxidant , biochemistry , immunology , biology , enzyme , in vitro
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 speices on human peripheral blood mononuclear cells (PBMC). PBMC were exposed to RPMI 1640 medium previously irradiated for up lo 60 min. Consistent dose‐dependent killing was observed at 24 h. Antioxidant studies indicated that H 2 O 2 was the effective species. Catalase, which specifically degrades H 2 O 2 , gave almost total protection against cell death, while superoxide dismutase (SOD), thiourea, and mannitol were largely ineffective. Addition of exogenous H 2 O 2 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 H 2 O 2 mediated its effects via OH* radicals, Analysis of lymphocyte subpopulalions showed that ROS caused a selective depletion, depending on the level of H 2 O 2 present. Low levels induced a speciftc loss of CD8 + cells, while higher concentrations caused significant loss of CD4 + T cells as well. slg + 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.