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Vitamin E (E) supplementation reverses the age associated decline in phosphorylation of the adaptor protein LAT in CD4 + T cells
Author(s) -
Marko Melissa G.,
Bunnell Stephen C.,
Huber Brigitte T.,
Meydani Simin Nikbin
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a558-b
Subject(s) - phosphorylation , t cell , immunological synapse , cd28 , t cell receptor , microbiology and biotechnology , biology , cell growth , zap70 , medicine , endocrinology , chemistry , immune system , immunology , biochemistry
T cell proliferation and interleukin (IL‐2) production declines with age. Engagement of the T cell receptor (TCR) by antigen, known as the immune synapse (IS), in coordination with phosphorylation of key signaling proteins, leads to increased IL‐2 synthesis and T cell proliferation. Defects in effective IS formation have been reported with age. We have shown that E supplementation improves IL‐2 secretion and cell proliferation of T cells from old mice. To determine the underlying mechanism we evaluated the effect of E on the total and phosphorylated expression of key signaling proteins, LAT, ZAP70 and Lck, and IS formation. Purified spleen CD4 + T cells from young (4 mo) and old (24 mo) C57BL/6 mice were incubated with E (46μM RRR‐α‐tocopherol) for 4 hrs and stimulated with anti‐CD3/anti‐CD28. The levels of total and phosphorylated LAT, ZAP70, and Lck were analyzed by western blot and effective IS was detected by confocal microscopy. LAT phosphorylation, but not total expression, was selectively and significantly reduced in the T cells of old mice 2 fold (p<0.05). E significantly enhanced LAT phosphorylation in T cells from old mice 1.7 fold (p<0.05), but E had no effect on that of young mice. Further, E supplementation of old T cells significantly increased effective IS formation (p<0.05). We conclude that aging hinders synchronized LAT phosphorylation and IS formation, impairing T cell signaling, IL‐2 production, and proliferation. E restores LAT phosphorylation and IS formation, leading to improved T cell proliferation in aged mice. Supported by NIA #R01AG009140‐10A1, USDA #58‐1950‐9‐001 and Unilever Health Institute fellowship.