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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #195400
Title: VITAMIN E (E) SUPPLEMENTATION REVERSES THE AGE ASSOCIATED DECLINE IN PHOSPHORYLATION OF THE ADAPTOR PROTEIN LAT IN CD4+ T CELLS

Author
item MARKO, MELISSA - TUFTS/HNRCA
item BUNNELL, STEPHEN - TUFTS UNIV SCH MED
item HUBER, BRIGITTE - TUFTS UNIV SCH MED
item Meydani, Simin

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2006
Publication Date: 4/1/2006
Citation: Marko, M.G., Bunnell, S.C., Huber, B.T., Meydani, S.N. 2006. Vitamin e (e) supplementation reverses the age associated decline in phosphorylation of the adaptor protein lat in cd4+ t cells. Federation of American Societies for Experimental Biology Conference.20:A558.

Interpretive Summary:

Technical Abstract: 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 (46 microM RRR-alpha-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.