Abstract
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.
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Zheng, L. et al. (1996). Mature T Lymphocyte Apoptosis in the Healthy and Diseased Immune System. In: Gupta, S., Cohen, J.J. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VI. Advances in Experimental Medicine and Biology, vol 406. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0274-0_24
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DOI: https://doi.org/10.1007/978-1-4899-0274-0_24
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