期刊
MOLECULAR ASPECTS OF MEDICINE
卷 33, 期 1, 页码 55-62出版社
ELSEVIER
DOI: 10.1016/j.mam.2011.11.002
关键词
Vitamin E; CD4+T cells; Aging; Signalosomes; Gene expression
CD4+T cells from aged humans or mice show significant reductions in IL-2 production upon activation. The resulting decreased proliferation is linked to higher risks of infection in the elderly. Several lines of evidence indicate that intrinsic defects preferentially affecting the naive subset of CD4+T cells contribute to this reduced IL-2 production. Comparison of the biochemical pathways that transduce activation signals from the T cell receptor to the IL-2 promoter in young and old CD4+T cells has demonstrated age-relate iimpairments at initial molecular events, in particular the phosphorylation of kinase:; and adapter proteins involved in the formation of signalosomes - complex multiprotein assemblies that provide the framework for effective signal transduction. Confocal microscopy has demonstrated a series of age-related impairments in effective immune synapse formation. Vitamin E can reverse many of these CD4+T cell age-associated defects, including reduced levels of phosphorylation of critical signaling/adapter proteins as well as defective immune synapse formation. Vitamin E also enhances IL-2 production, expression of several cell cycle control proteins, and proliferation. Although the precise mechanisms underlying this effect are not understood, it is possible that this antioxidant lipophilic vitamin can prevent the propagation of polyunsaturated fatty acid peroxidation in the cell membrane, influence the biochemical characteristics of specific lipid bilayer microdomains involved in signal transduction, modulate the activity of kinases/phosphatases, or interact with h intracellular receptors. (C) 2011 Elsevier Ltd. All rights reserved.
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