Cell death and longevity: implications of Fas-mediated apoptosis in T-cell senescence.
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-fas transgene produced undesirable side-effects to aged 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.[1]References
- Cell death and longevity: implications of Fas-mediated apoptosis in T-cell senescence. Mountz, J.D., Wu, J., Zhou, T., Hsu, H.C. Immunol. Rev. (1997) [Pubmed]
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