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 PKC&theta; from cytoplasm to the site of T-cell interaction with antigen-presenting cells may underlie downstream defects in the activation cascade.
Miller
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RA
Department of Pathology and Geriatrics Center, University of Michigan School of Medicine, Institute of Gerontology, and Ann Arbor VA Medical Center, Ann Arbor, MI 48109-0940, USA. millerr@umich.edu
D000375:Aging / Q000276:immunology*; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D000941:Antigens; D017252:CD3 Complex / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D000074121:Protein Kinase C-theta; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D000941:Antigens; D017252:CD3 Complex; D007527:Isoenzymes; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse; D019908:Proto-Oncogene Proteins c-raf; C076233:PRKCQ protein, human; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases