Background:Intensive care for patients with human immunodeficiency virus is common, costly, and associated with high morbidity. Accurate and up-to-date outcome and prognostic data are needed to effectively counsel patients and to make difficult decisions regarding admission to the intensive care unit.

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.

The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.

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