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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Lenardo MJ. Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Nature 1991; 353 (6347): 858–61.
Critchfield JM, Racke MK, Zuniga-Pflucker JC, et al. T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis. Science 1994; 263 (5150): 1139–43.
Critchfield JM, Boehme SA, Lenardo Mi. The regulation of antigen-induced apoptosis in mature T lymphocytes. Apoptosis and the Immune Response 1995; Wiley-Liss, Inc.: 55–114.
Lenardo MJ, Boehme SA, Chen L, et al. Autocrine feedback death and the regulation of mature T lymphocyte antigen responses. Intern. Rev. Immunol. 1995; 13: 115–134.
Willerford DM, Chen J, Ferry JA, Davidson L, Ma A, Alt FW. Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity 1995; 3 (4): 521–30.
Kneitz B, Herrmann T, Yonehara S, Schimpl A. Normal clonal expansion but impaired Fas-mediated cell death and anergy induction in interleukin-2-deficient mice. Eur J Immunol 1995; 25 (9): 2572–7.
Adachi M, Watanabe-Fukunaga R, Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of 1pr mice. Proc Natl Acad Sci U S A 1993; 90 (5): 1756–60.
Takahashi T, Tanaka M, Brannan CI, et al. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 1994; 76 (6): 969–76.
Zheng L, Fisher G, Miller RE, Peschon J, Lynch DH, Lenardo MJ. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature 1995; 377 (6547): 348–51.
Dhein J, Walczak H, Baumler C, Debatin KM, ‘Crammer PH. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) [see comments]. Nature 1995; 373 (6513): 438–41.
Brunner T, Mogil RJ, LaFace D, et al. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas [see comments]. Nature 1995; 373 (6513): 441–4.
Ju ST, Panka DJ, Cui H, et al. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation [see comments]. Nature 1995; 373 (6513): 444–8.
Smith CA, Farrah T, Goodwin RG. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 1994; 76 (6): 959–62.
Nagata S, Golstein P. The Fas death factor. Science 1995; 267 (5203): 1449–56.
Beyaert R, Fiers W. Molecular mechanisms of tumor necrosis factor-induced cytotoxicity. What we do understand and what we do not. Febs Lett 1994; 340 (1–2): 9–16.
Reid T, Louie P, Heller RA. Mechanisms of tumor necrosis factor cytotoxicity and the cytotoxic signals transduced by the p75-tumor necrosis factor receptor. Circ Shock 1994; 44 (2): 84–90.
Grell M, Zimmermann G, Hulser D, Pfizenmaier K, Scheurich P. TNF receptors TR60 and TR80 can mediate apoptosis via induction of distinct signal pathways. J Immunol 1994; 153 (5): 1963–72.
Rothe M, Wong SC, Henzel WJ, Goeddel DV. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 1994; 78 (4): 681–92.
Tartaglia LA, Weber RF, Figari IS, Reynolds C, Palladino M, Jr., Goeddel DV. The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proc Natl Acad Sci U S A 1991; 88 (20): 9292–6.
Rothe M, Sarma V, Dixit VM, Goeddel DV. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 1995; 269 (5229): 1424–7.
Tartaglia LA, Pennica D, Goeddel DV. Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J Biol Chem 1993; 268 (25): 18542–8.
Vandenabeele P, Declercq W, Vanhaesebroeck B, Grooten J, Fiers W. Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells. J Immunol 1995; 154 (6): 2904–13.
Grell M, Scheurich P, Meager A, Pfizenmaier K. TR60 and TR80 tumor necrosis factor (TNF)-receptors can independently mediate cytolysis. Lymphokine Cytokine Res 1993; 12 (3): 143–8.
Bigda J, Beletsky I, Brakebusch C, et al. Dual role of the p75 tumor necrosis factor (TNF) receptor in TNF cytotoxicity. J Exp Med 1994; 180 (2): 445–60.
Rothe M, Pan M-G, Henzel WJ, Ayres TM, Goeddel DV. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 1995; 83 (7): 1243–1252.
Sneller MC, Straus SE, Jaffe ES, et al. A novel lymphoproliferative/autoimmune syndrome resembling murine 1pr/gld disease. The Journal of Clinical Investigation 1992; 90: 334–341.
Fisher GH, Rosenberg FJ, Straus SE, et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 1995; 81 (6): 935–46.
Weisdorf SA, Krivit W. Paucity of splenic germinal centers: A new and unique splenomegaly syndrome including dysfunctional immune system. Clincal Immunology and Immunopathology 1982; 23: 492–500.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer Science+Business Media New York
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-1-4899-0274-0_24
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-0276-4
Online ISBN: 978-1-4899-0274-0
eBook Packages: Springer Book Archive