Impairment of signal transduction in T cells from old mice

Mech Ageing Dev. 1997 Feb;93(1-3):131-44. doi: 10.1016/s0047-6374(96)01837-4.

Abstract

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.

MeSH terms

  • Aging / immunology*
  • Animals
  • Calcium / metabolism
  • Clone Cells
  • Diglycerides / metabolism
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Interleukin-2 / pharmacology
  • Kinetics
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Receptor-CD3 Complex, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Signal Transduction*
  • Spleen / growth & development
  • Spleen / immunology
  • Spleen / radiation effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Type C Phospholipases / metabolism

Substances

  • Diglycerides
  • Interleukin-2
  • Phosphatidylinositol 4,5-Diphosphate
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Inositol 1,4,5-Trisphosphate
  • Type C Phospholipases
  • Tetradecanoylphorbol Acetate
  • Calcium