A 5- to 10-fold decline was observed in the proliferative activity of
T cells stimulated with anti-CD3 mAb between young and old mice. Howev
er, the number of CD3 molecules on the T cell surface was almost compa
rable between young and old T cells. The formation of the second messe
nger such as inositol triphosphate (IP3) and diacylglycerol (DAG) afte
r mitogenic stimulation decreased in old T cells as compared with youn
g ones. The activity of phospholipase C (PLC), which is responsible fo
r the liberation of IP3 and DAG from phosphatidylinositol-4,5-bisphosp
hate (PIP2) was not different between young and old T cells. The conte
nt of PIP2 in the membrane was also comparable between young and old T
cells. These findings have suggested that the age-related decline in
the proliferative activity of T cells could be due to impairment of in
tracellular signal transduction, probably in the pathway somewhere bet
ween TCR and PLC.