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Cell death and longevity: implications of Fas‐mediated apoptosis in T‐cell senescence
Author(s) -
Mountz John D.,
Wu Jianguo,
Zhou Tong,
Hsu HuiChen
Publication year - 1997
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1997.tb01024.x
Subject(s) - apoptosis , biology , senescence , programmed cell death , microbiology and biotechnology , t cell , transgene , immune system , genetically modified mouse , cell cycle , cell , immunology , genetics , gene
Summary: Two prominent features of immune senescence are altered T‐cell phenotype and reduced T‐cell response. We have previously shown that T‐cell senescence is greatly reduced in CD2‐ fas transgenic mice, in which the Fas apoptosis molecule is constantly expressed on T cells. Using a different experimental approach, the relationship between T‐cell senescence And apoptosis was analyzed on human peripheral blood mononuclear cells. The results indicate that there was increased apoptosis of CD45RO − (CD45RA + ) T cells upon activation. We propose that this could account for the increase in CD45RO + “memory” T cells with aging in humans. T‐cell responsiveness remained high in CD2‐ fas transgenic aged mice, but there was no increase in overall life span of these mice. Increased T‐cell responsiveness was associated with an increased acute‐phase response and serum amyloid A deposition in the glomerulus of aged CD2‐ fas transgenic mice. Therefore, restoration of the T‐cell immune function using a CD2‐fus transgene produced undesirable side‐effects transgenic mice. In addition to its role in activation‐Induced cell death. Fas‐mediated apoptosis may be important in deleting T cells in response to DNA damage. It may also inhibit cell‐cycle progression by cleaving various kinases and DNA repair enzymes. We observed that cell lines derived from human premature aging diseases have a higher sensitivity to Fas mediated apoptosis. The implications of these observations are discussed.