Effect of aging on T lymphocyte activation.

Studies of the early stages of T-cell activation reveal that T cells from aged mice show multiple abnormalities within the first few minutes after stimulation, including decline in the activation of the Raf-1/MEK/ERK kinases and in JNK protein kinase. Zap-70 kinase associated with the CD3zeta chain shows a 2-fold increase with age in resting CD4 T cells, despite a three-fold decline with age in the levels of tyrosine phosphorylation of CD3zeta; nonetheless, there is no effect of aging on Zap-70 kinase function in activated T cells as measured by in vitro kinase methods. Age-related impairment of the translocation of PKCθ from cytoplasm to the site of T-cell interaction with antigen-presenting cells may underlie downstream defects in the activation cascade.