ABNORMALITY IN THE EARLY SIGNAL-TRANSDUCTION PATHWAY IS RESPONSIBLE FOR THE IMPAIRED PROLIFERATIVE RESPONSE AND LOW K-CELL CLONE BY STIMULATION WITH ANTI-CD3 ANTIBODY( CURRENT IN A T)

Two T-cell clones were established from young and old C57BL/6 mice, re spectively. The proliferative response to anti-CD3 stimulation was sig nificantly greater in the young (YT5) than in the old (OT13) T cell cl one. However, a similar high response was observed in both T-cell clon es upon stimulation with phorbol myristate acetate (PMA) and ionomycin (INM). The calcium-dependent K+ current (IK(Ca)) was recorded with th e patch-clamp method in these T-cell clones. With anti-CD3 stimulation , the amplitude of the outward K+ current was significantly lower in O T13 than in YT5 cells. With stimulation with PMA and INM, however, no significant difference in IK(Ca) was obtained between the two types of cells. The level of proliferative response of T-cells to mitogens was well reflected by the amplitude of IK(Ca). Some abnormality in the ea rly pathway of signal transduction, which led to the intracellular Ca2 + influx, appears to be responsible for the impaired proliferation of the old T-cell clone.