Author
MARKO, MELISSA - JM USDA HNRCA @ TUFTS | |
PANG, HOAN-JEN - JM USDA HNRCA @ TUFTS | |
BUNNELL, STEPHEN - TUFTS SCHOOL OF MEDICINE | |
AZZI, ANGELO - JM USDA HNRCA @ TUFTS | |
HUBER, BRIGITTE - TUFTS SCHOOL OF MEDICINE | |
Meydani, Simin |
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 4/29/2009 Publication Date: 5/1/2009 Citation: Marko, M., Pang, H.E., Bunnell, S.C., Azzi, A., Huber, B.T., Meydani, S. 2009. Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice. Journal of Nutrition. 139:1192-1197. Interpretive Summary: T cell function is necessary to fight infection and declines with aging. Vitamin E supplementation restores T cell production in mice and humans. To understand the mechanism, we evaluated the effect of E on early molecular events associated with T cell receptors. One such molecule is LAT (linker for the activation of T cell) production which plays a critical role in this mechanism. Results showed that in T cells of aged mice, LAT is not properly activated (is less phosphorylated). This results in less expression of important genes for T cell function such as cytokine interleukin 2 (IL-2). Furthermore, we showed that vitamin E supplementation increases LAT activation (more phosphorylated) resulting in more IL-2 expression and better ability of T cells to proliferate, an important measure of their functionality. This finding is important in the aging process since it suggests a model to determine the underlying cause of T cell defects that occur with aging and the potential to reverse this problem with the use of vitamin E supplementation. Technical Abstract: Supplemental vitamin E restores age-related defects in IL-2 production, T cell proliferation, and immune synapse formation. Here, we evaluated the effect of vitamin E on TCR-proximal signaling events. In aged murine CD4+ T cells stimulated via CD3 and CD28, tyrosine 191 of the adaptor protein LAT was hypo-phosphorylated, and supplementation with vitamin E eliminated this difference in the tyrosine phosphorylation of LAT. Using a flow cytometric assay, we show, for the first time, that the age-related differences in the activation-induced phosphorylation of LAT are observed in both the naïve and memory T cell subsets. In both cases, supplementation with vitamin E eliminated the age-related differences in LAT phosphorylation. The fraction of LAT entering the membrane compartment was not altered by either age or vitamin E supplementation. Furthermore, neither age nor vitamin E had a significant effect on phosphorylation of Lck and Zap-70. Our observations indicate that age- and vitamin E-associated changes in LAT phosphorylation are not caused by alterations in activation states of upstream kinases Lck and Zap-70. |