Impairment of signal transduction in T cells from old mice.
T cells from old mice showed impaired proliferative response to antigenic stimulation. To understand the mechanism underlying the age-related impairment of T cell functions, the signal transduction pathway was examined and compared between T cells from young and old mice, and between T cell clones established from a young and old mouse. The age-related changes in T cells were as follows: (1) reduction in the expression and the activation of protein tyrosine kinases associated with T cell receptor (TCR) after antigenic stimulation; (2) reduced phosphorylation of phospholipase C gamma 1 (PLC gamma 1); (3) reduced production of second messengers such as inositoltrisphosphate (IP3) and diacylglycerol (DAG); and (4) reduced influx of Ca2+ ion. Thus, a T cell clone established from an old mouse showed impaired proliferation by stimulation 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 myristate (PMA) plus ionomycin (INM). However, splenic T cells freshly prepared from old mice did not show full recovery by the same treatment. The results indicate that one major blockade in the signal transduction of T cells from old mice is present in the pathway just after TCR, but besides this, the blockade is also present in multiple sites down-stream, which can not be bypassed by stimulation with PMA plus INM.
Utsuyama
M
M
Department of Pathology and Immunology, School of Medicine, Tokyo Medical and Dental University, Japan.
Wakikawa
A
A
Tamura
T
T
Nariuchi
H
H
Hirokawa
K
K
D000375:Aging / Q000276:immunology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D004075:Diglycerides / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D015398:Signal Transduction; D013154:Spleen / Q000254:growth & development / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D007376:Interleukin-2; D019269:Phosphatidylinositol 4,5-Diphosphate; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium