Abstract：
:Aged animals and humans exhibit a decreased T-cell activation response although they also exhibit increased susceptibility to responses to self-antigens and a loss of self-tolerance. The age-related alteration in T-cell reactivity, polyclonal expansion of T cells, and enhanced production of autoantibodies may reflect the numerous age-associated alterations in the T-cell arm of the immune system that have been revealed in numerous studies. These studies suggest that subpopulations of T cells are not deleted appropriately in older animals. They further suggest that an age-related impairment of Fas/Fas ligand (FasL)-mediated apoptosis - which plays a major role in activation-induced cell death (AICD) of T cells - may contribute to compromised regulation of the immune system. The likely mechanisms that may lead to impaired induction of FasL in AICD senescent T cells include an age-related shift from the apoptosis-sensitive T-helper 1 cell (Th1) response to the AICD-resistant Th2 response, aberrant T-cell receptor/CD3 downstream-signaling pathways, and altered CD28/B7-mediated T-cell costimulatory signals. Pathologically, accumulation of AICD-senescent T cells is associated with a defective cytotoxic T lymphocyte response and generation of autoreactive T cells. Based on the accumulating evidence, we propose that the emergence of the FasL(lo) AICD-senescent T cells is not only an effect of immune aging but also an important cause of T-cell proliferative senescence in both humans and mice.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Hsu HC,Scott DK,Mountz JDdoi
10.1111/j.0105-2896.2005.00270.xkeywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
130-46eissn
0105-2896issn
1600-065Xpii
IMR270journal_volume
205pub_type
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