Molecular mechanism of the impairment in activation signal transduction inCD4(+) T cells from old mice

It is well known that IL-2 production of CD4(+) T cells from old mice (old T cells) is impaired. In this study, we have examined TCR complex zeta chai n expression of old T cells and their TCR downstream signal transduction pa thways stimulated with anti-CDS, Activation of protein tyrosine kinases, Fy n and ZAP-70, and turnover of inositol phosphates stimulated with anti-CDS were severely impaired in old T cells, although levels of these proteins we re comparable to those in young T cells. Increase in intracellular Ca2+ con centration in old T cells was also impaired. Old T cells starting the Ca2oscillation by the anti-CD3 stimulation were severely decreased in number a nd the oscillation waves were broader in shape. T cells with xi-Fc epsilon R gamma heterodimer in the TCR-CD3 complex were increased in proportion in old T cells with a concomitant decrease in the T cells with xi-xi homodimer , The density of the TCR-CD3 complex on old T cells was confirmed to be com parable to that on young T cells. The impairment in TCR downstream signal t ransduction pathways and the increase in xi-Fc epsilon R gamma heterodimer in the TCR-CD3 complex were confirmed to be the situation in Th1 clones est ablished from old mice. These results indicate that old T cells are impaire d in response to TCR stimulation, because T cells with the TCR-CD3 complex containing the zeta-Fc epsilon R gamma heterodimer are increased in proport ion in old T cells.