Mature T lymphocyte apoptosis in the healthy and diseased immune system

We have been studying a feedback regulatory mechanism termed propriocidal regulation that induces mature peripheral T cells to undergo apoptosis during an antigen response. We proposed this mechanism in order to account for two observations. First, we observed that mature T lymphocytes can be triggered to undergo apoptosis following T cell receptor (TCR) ligation 1,2, for a reviews see 3, 4. This finding challenged the prevailing idea that only immature T cells in the thymus could exhibit an apoptotic response to TCR stimulation. Second, we made the surprising observation that interleukin-2 (IL-2) was the principal influence that caused peripheral T lymphocytes to become susceptible to TCR-induced apoptosis1. This led to the notion that antigen-induced death was the end-result of a feedback loop. We conceived that strong, repeated antigen stimulation would first initiate a robust proliferative reaction and then induce the death of T cells following their effector response. This would decrease the number of specifically-responding T cells and the magnitude of the response to subsequent antigen challenge. The consequence of this feedback loop is that an unregulated geometric expansion of activated T lymphocytes and their attendant toxicities would be prevented. Thus, propriocidal regulation entails immune regulation by the programmed cell death of mature T cells. This provides a means for antigen-specific, extrathymic immunological tolerance.