Activation-Induced Cell Death of T Cells in Human Aging

  • Ewa Sikora
  • Agnieszka Brzezińska
Living reference work entry


The elimination of expanded T cells at the end of immune response is crucial to maintain homeostasis and avoid any uncontrolled inflammation. Resting mature T lymphocytes when activated via their antigen-specific receptor (TCR) and CD28 coreceptor start to proliferate and acquire resistance to apoptosis. Reactivation of T cells induces expression of CD95L, which after binding to CD95 surface-expressed death receptor, triggers signaling pathway to apoptosis. The process is called activation-induced cell death (AICD). In executing AICD, receptor-dependent apoptotic pathway overlaps with mitochondrial signaling to apoptosis. Immunosenescence leads to the shrinkage of T-cell repertoire due to the reduction of naïve cells and accumulation of oligoclonal CD8+ and, to a lower extent, CD4+ cells, which are mainly CD95-positive and CD28-negative. CD28− cells dominate not only in elderly people, but their presence has also been linked to autoimmune disease, AIDS, and age-related disorders or decreased efficacy of vaccination. Propensity of CD28− cells to undergo AICD, and generally, apoptosis changes with age. However, collected data so far are inconclusive as they show an increased, unchanged, or decreased propensity to apoptosis in the elderly in comparison with young individuals. Recently, a definite involvement of autophagy and necroptosis in homeostasis of T cells has been recognized; however, their role in the termination of the adaptive immune response is still poorly known, especially in aging. However, it can be expected that future studies on necroptotic and autophagic cell death will clarify the so far inconsistent data concerning age-dependent changes in AICD.


Apoptosis Autophagy CD28 CD95 Necroptosis 



It is to acknowledge that the part of this chapter was already published in Elsevier Journal as the following article by Ewa Sikora (2015).


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental BiologyPolish Academy of SciencesWarsawPoland

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