The molecular aspects of T-cell activation and subsequent progression through the cell cycle are investigated using the murine model to establish a basis for the immunodeficiencies associated with advancing age. Comparative studies of polyclonally activated G0 T-cells from young and old C57Bl/6 mice showed that a significantly higher portion of cells derived from the old mice underwent apoptotic cell death which was restricted to the G1 phase of the cell cycle. Irrespective of age apoptosis involved both CD4+ and CD8+ cells. There were significantly higher numbers of CD4+ memory cells within the G0 T-cells from the old mice and was identified as the major apoptotic cell population. In addition to an increase in apoptosis in the activated T-cells from the old mice, a significantly higher number of viable activated cells failed to complete progression through the G1 phase of the cell cycle. Initial evidence suggest that the expression of the genes encoding the G1 cyclin-dependent kinases and the partner cyclins is not significantly different from that observed in T-cells from young mice. The kinetics of the kinase expression in the T-cells from the old mice differs from that observed in young animals suggesting that the family of cyclin-dependent kinase inhibitors may be involved in regulating the kinase activity in the cells from the old mice. Northern analysis of the kinetic expression of specific mRNA for two of these inhibitors i.e. p21 and p27, showed prolonged synthesis in the T-cells from the old mice.
