IMPAIRMENT OF SIGNAL-TRANSDUCTION IN T-CELLS FROM OLD MICE

T cells from old mice showed impaired proliferative response to antige nic stimulation. To understand the mechanism underlying the age-relate d impairment of T cell functions, the signal transduction pathway was examined and compared between T cells from young and old mice, and bet ween T cell clones established from a young and old mouse. The age-rel ated changes in T cells were as follows: (1) reduction in the expressi on and the activation of protein tyrosine kinases associated with T ce ll receptor (TCR) after antigenic stimulation; (2) reduced phosphoryla tion of phospholipase C gamma 1 (PLC gamma 1); (3) reduced production of second messengers such as inositoltrisphosphate (IP3) and diacylgly cerol (DAG); and (4) reduced influx of Ca2+ ion. Thus, a T cell clone established from an old mouse showed impaired proliferation by stimula tion with anti-CD3 antibody, but was fully activated to the level of a T cell clone from a young mouse by stimulation with phorbol acetate m yristate (PM,4) plus ionomycin (INM). However, splenic T cells freshly prepared from old mice did not show full recovery by the same treatme nt. The results indicate that one major blockade in the signal transdu ction of T cells from old mice is present in the pathway just after TC R, but besides this, the blockade is also present in multiple sites do wn-stream, which can not be bypassed by stimulation with PMA plus INM. (C) 1997 Elsevier Science Ireland Ltd.