Studies of the early stages of T-cell activation reveal that T cells from a
ged mice show multiple abnormalities within the first few minutes after sti
mulation, including decline in the activation of the Raf-1/MEK/ERK kinases
and in JNK protein kinase. Zap-70 kinase associated with the CD3 zeta chain
shows a 2-fold increase with age in resting CD4 T cells, despite a three-f
old decline with age in the levels of tyrosine phosphorylation of CD3 zeta;
nonetheless, there is no effect of aging on Zap-70 kinase function in acti
vated T cells as measured by in vitro kinase methods. Age-related impairmen
t of the translocation of PKC theta from cytoplasm to the site of T-cell in
teraction with antigen-presenting cells may underlie downstream defects in
the activation cascade. (C) 2000 Elsevier Science Ltd. All rights reserved.