title: Vitamin E, signalosomes and gene expression in T cells.
abstract: 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 naïve 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-related impairments at initial molecular events, in particular the phosphorylation of kinases 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 intracellular receptors.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. alberto.molano_acevedo@tufts.edu
authors.forename: Alberto
authors.initials: A
authors.lastname: Molano
authors.forename: Simin Nikbin
authors.initials: SN
authors.lastname: Meydani
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013107:Sphingolipids / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D013107:Sphingolipids; D014810:Vitamin E