PROTEIN OR RNA-SYNTHESIS INHIBITION INDUCES APOPTOSIS OF MATURE HUMAN CD4+ T-CELL BLASTS

Proliferating human T lymphocytes were found to undergo spontaneous programmed cell death (apoptosis) when removed from the source of stimulation or after a prolonged period of stimulation. Apoptosis was demonstrated in these cells by the appearance of DNA fragments with a characteristic pattern of approximately 200 base pair multiples, indicative of internucleosomal DNA cleavage. We tested whether this process was dependent on protein or RNA synthesis using the inhibitors cycloheximide or actinomycin D. In contrast with previous studies on thymocytes, we found that these inhibitors actually accelerated apoptosis of mature CD4+ T cells instead of the expected inhibition. These results indicate that RNA and/or protein synthesis are not rigid requirements for the induction of apoptosis in T cells, and suggest that ongoing synthesis of either a 'death-suppressor' protein or its receptor may be required to prevent the spontaneous apoptosis of activated T cells.