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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #201739
Title: Vitamin E (E) supplementation reverses the age associated decline in phosphorylation of the adaptor protein LAT in CD4+ T cells of old mice

Author
item MARKO, MELISSA - TUFTS/HNRCA
item BUNNELL, STEPHEN - TUFTS UNIVERSITY
item HUBER, BRIGITTE - TUFTS UNIVERSITY
item Meydani, Simin

Submitted to: American Aging Association
Publication Type: Abstract Only
Publication Acceptance Date: 6/2/2006
Publication Date: 6/2/2006
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 of old mice. AGE. 28(1):12-13.

Interpretive Summary:

Technical Abstract: T cell proliferation and interleukin (IL-2) production declines with age. Engagement of the T cell receptor (TCR) by antigen (Ag), 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 vitamin E supplementation improves IL-2 secretion and cell proliferation of T cells from old mice. To determine the underlying mechanisms we evaluated the effect of E on IS formation, and the total and phosphorylated expression of key signaling proteins LAT, Lck, and Zap-70. Purified spleen CD4+ T cells from young (4 mo) and old (24 mo) C57BL/6 mice were incubated with E (46microM RRR-alpha-tocopherol) for 4 hrs and stimulated with anti-CD3/anti-CD28. Effective IS was detected by confocal microscopy and the levels of total and phosphorylated LAT, Lck, and Zap-70 were analyzed by western blot. E supplementation of old T cells significantly increased effective IS formation (p<0.05). Further, LAT phosphorylation, but not total expression, was selectively and significantly reduced in the T cells of old mice (2 fold reduction, p<0.05). E significantly enhanced LAT phosphorylation in T cells from old mice (1.7 fold increase, p<0.05), but had no effect on that of T cells from young mice. This indicates that aging hinders synchronized IS formation and LAT phosphorylation, impairing T cell signaling, IL-2 production, and proliferation. E supplementation restores IS and LAT phosphorylation, leading to improved T cell proliferation and IL-2 production in aged mice. This is the first demonstration of a nutrient-induced reversal of a defective early signaling event in aged T cells. These findings may have significant implications for understanding the underlying mechanisms and development of strategies to prevent age-related T cell dysfunction. Supported by NIA #R01AG009140-10A1, USDA #58-1950-9-001 and Unilever Health Institute fellowship.