Mature T Lymphocyte Apoptosis in the Healthy and Diseased Immune System

  • Lixin Zheng
  • Galen Fisher
  • Behazine Combadiere
  • Felicita Hornung
  • David Martin
  • Clara Pelfrey
  • Jin Wang
  • Michael Lenardo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

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.

Keywords

Tumor Necrosis Factor Receptor Lymphocyte Apoptosis Diseased Immune System Generalize Lymphoproliferative Disease Viable Cell Recovery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Lixin Zheng
    • 1
  • Galen Fisher
    • 1
  • Behazine Combadiere
    • 1
  • Felicita Hornung
    • 1
  • David Martin
    • 1
  • Clara Pelfrey
    • 1
  • Jin Wang
    • 1
  • Michael Lenardo
    • 1
  1. 1.Laboratory of ImmunologyNational Institute of Allergy and Infectious Diseases National Institutes of HealthBethesdaUSA

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