Are NK cells more vulnerable to cell death than T cells?

Details

The researchers investigated apoptosis—programmed cell death—in human NK cells and T cells using laboratory incubation and experiments that induced or inhibited apoptosis. Human NK cells with the CD3−/56+ phenotype developed features of apoptosis after incubation with autologous monocytes, meaning monocytes from the same individual. The evidence included apoptotic nuclear morphology, DNA degradation into oligonucleosomal fragments, and reduced nuclear intercalation of propidium iodide. In contrast, T cells with the CD3+/56− phenotype remained non-apoptotic.

Catalase, a hydrogen peroxide scavenger, prevented monocyte-induced apoptosis in NK cells. However, superoxide dismutase, a superoxide anion scavenger; the hydroxyl radical scavengers mannitol and deferoxamine; and the hypochlorous acid scavenger taurine did not prevent apoptosis. Sodium azide, a myeloperoxidase inhibitor, substantially reduced monocyte-induced apoptosis in NK cells.

Externally supplied hydrogen peroxide induced apoptosis in both NK cells and T cells at concentrations exceeding “1 microns,” the unit as reported in the abstract. Hydrogen peroxide-induced apoptosis occurred independently of protein or mRNA synthesis and was blocked by the endonuclease inhibitor aurin tricarboxylic acid. Herbimycin A also inhibited oxidatively induced apoptosis in NK cells, indicating that this apoptosis depended on protein kinases.

Inducing apoptosis in T cells required two to five times more hydrogen peroxide than in NK cells. NK cells were also considerably more susceptible than T cells to apoptosis induced by the topoisomerase II inhibitor etoposide or by gamma irradiation.

The researchers concluded that monocyte-derived reactive oxygen metabolites kill NK cells through apoptosis, and that NK cells are unusually sensitive to both oxidatively and non-oxidatively induced apoptosis.