Activation-driven T cell death. I. Requirements for de novo transcription and translation and association with genome fragmentation

Abstract

We have observed that stimuli that are mitogenic for normal T cells can induce cell death in transformed T cell hybridomas. "Activation-driven cell death" can be triggered by the presentation of appropriate Ag as well as by treatment with lectins and antibodies specific for the T cell Ag receptor complex and other activation structures on the T cell surface, such as Thy-1 and Ly-6. The activation-driven lethal process is cell autonomous, is associated with a fragmentation of the cell's genome characteristic of the "suicide process" induced in immature T cells by glucocorticoids and in target cells by cytotoxic T lymphocytes, and is dependent upon transcription and translation, presumably associated with the expression of new gene products. We hypothesize that activation-driven cell death may be involved in vivo in the clonal deletion of auto-reactive T cells during T cell ontogeny.