Differential sensitivity of naïve and subsets of memory CD4+ and CD8+ T cells to hydrogen peroxide-induced apoptosis

Abstract

CD4 þ and CD8 þ 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 þ and CD8 þ T cells are sensitive to hydrogen peroxide (H 2 O 2 )-induced apoptosis, whereas effector memory CD4 þ and CD8 þ T cells are relatively resistant to H 2 O 2 -induced apoptosis. Apoptosis in naïve and central memory CD4 þ and CD8 þ 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 H 2 O 2 -induced apoptosis in both naïve and central memory CD4 þ and CD8 þ T cells. Furthermore, VDAC inhibitor 4,4 0 -diisothiocynostilbene-2,2 0 -disulfonic acid blocked H 2 O 2 -induced apoptosis. These data demonstrate that H 2 O 2 induces apoptosis preferentially in human naïve and central memory CD4 þ and CD8 þ T cells via the mitochondrial pathway by regulating intracellular GSH and the expression of Bax and VDAC.

Effect of activated human polymorphonuclear leucocytes on T lymphocyte proliferation and viability

“…Furthermore, if arginase activity is inhibited at the time of PMN activation, the proportion of non‐viable T cells is further increased via a process also involving H 2 O 2 generation. Differential sensitivity of T‐cell subsets to H 2 O 2 ‐mediated cell death has been reported previously and may explain why only a proportion of T cells were susceptible to PMN act ‐mediated cell death . This differential sensitivity may also explain why the presence of ABAH, which inhibits a major pathway of H 2 O 2 consumption and may therefore increase its levels, induced increased cell death in pre‐activated cells but not purified circulating T cells.…”

Relationship Between Redox Status and Cell Fate in Immunity and Autoimmunity

“…According to the results by Takahashi et al (169), a higher expression of the GSH molecule has been found in the naive T-cell subset as compared with the memory T-cell subset (46). Different results were reported by Gupta et al (57), who observed that H 2 O 2 induced apoptosis preferentially in naive T cells and central memory T cells as compared with effector memory T cells via a reduction in GSH levels. Overall, these data, although contrasting, show that distinct T-cell subsets have differential susceptibility to oxidative stress-induced apoptosis, and this susceptibility is associated with intracellular GSH.…”

HIV-1 Induces DCIR Expression in CD4+ T Cells

“…Given that H 2 O 2 induces also necrosis and mediates apoptosis primarily via a caspase-dependent pathway [39], [40], we performed experiments with Z-VAD-FMK. A pre-treatment with Z-VAD-FMK prevented DCIR expression in activated CD4 + T cells after H 2 O 2 stimulation (i.e.…”