Differential sensitivity of naïve and subsets of memory CD4+ and CD8+ T cells to hydrogen peroxide-induced apoptosis.
CD4+ and CD8+ memory T cells are identified into central and effector memory subsets, which are characterized by distinct homing patterns and functions. In this investigation, we show that naïve and central memory CD4+ and CD8+ T cells are sensitive to hydrogen peroxide (H2O2)-induced apoptosis, whereas effector memory CD4+ and CD8+ T cells are relatively resistant to H2O2-induced apoptosis. Apoptosis in naïve and central memory CD4+ and CD8+ is associated with the release of cytochrome c and activation of caspase-9 and caspase-3, upregulation of Bax and voltage-dependent anion channel (VDAC) expression, and decreased intracellular glutathione (GSH). In vitro GSH and a superoxide dismutase mimetic Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin inhibited H2O2-induced apoptosis in both naïve and central memory CD4+ and CD8+ T cells. Furthermore, VDAC inhibitor 4,4'-diisothiocynostilbene-2,2'-disulfonic acid blocked H2O2-induced apoptosis. These data demonstrate that H2O2 induces apoptosis preferentially in human naïve and central memory CD4+ and CD8+ T cells via the mitochondrial pathway by regulating intracellular GSH and the expression of Bax and VDAC.
Gupta
S
S
Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA. sgupta@uci.edu
Young
T
T
Yel
L
L
Su
H
H
Gollapudi
S
S
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007156:Immunologic Memory; D008665:Metalloporphyrins / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D020169:Caspases; D005978:Glutathione