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A poptosis is a morphologically distinct form of cell death involved in many physiological and pathological processes. Expression of the CD95 (APO-1/Fas) ligand (CD95L) is critically involved in activation-induced cell death (AICD) of activated T cells. Here we show that the natural free radical scavenger vitamin E suppresses the activity of the transcription factors NF-κB and AP-1, thus blocking expression of CD95L and preventing T cell AICD. Since AICD is a major cause of T cell depletion in AIDS, we examined 35 HIV-1–positive individuals and found that their T cells are more susceptible to AICD than are T cells isolated from healthy controls. Administration of vitamin E suppresses CD95L mRNA expression and protects T cells of HIV-1–infected individuals from CD95-mediated apoptosis. This evidence that vitamin E can affect T cell survival may merit further clinical investigation.