CLINICAL-FEATURES ASSOCIATED WITH CORRECTION OF T-CELL SENESCENCE - INCREASED ACUTE-PHASE RESPONSE, AMYLOIDOSIS AND ARTHRITIS

Two prominent features associated with immunosenescence are thymic inv olution and altered T-cell phenotype and responsiveness, Fire have sho wn previously that in CD2-fas transgenic mice, in which the Fas apopto sis molecule is constituatively expressed on T cells, T-cell senescenc e is greatly reduced, Using a different experimental approach, the rel ationship between T-cell senescence and apoptosis was analyzed on huma n PBMCs. The results indicate that there was increased apoptosis of CD 45RO(-) (CD45RA(+)) T cells upon activation, We propose that this coul d account for the increase in CD45RO(+) 'memory' T cells with aging in humans, Together these results are consistent with the notion that T- cell senescence is associated with altered apoptosis and decreased T-c ell responsiveness. T-cell responsiveness remained high in CD2-fas tra nsgenic aged mice, but there was no increase in overall life span of t he mice, Increased T-cell responsiveness was associated with an increa sed acute-phase response and amyloid A deposition in the glomerulus of these mice, These data suggest that restoration of the T-cell immune function in aged individuals must be carried out in concert with corre ction of other immune factors that down modulate the acute-phase respo nse to prevent undesirable side-effects. (C) 1997 Elsevier Science Ltd . All rights reserved.