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Age-Associated Decline in Effective Immune Synapse Formation of CD4⁺ T Cells Is Reversed by Vitamin E Supplementation¹

Melissa G. Marko^2,*, Tanvir Ahmed^2,3,*, Stephen C. Bunnell, Dayong Wu^*, Heekyung Chung^*, Brigitte T. Huber and Simin Nikbin Meydani^4,*,

^* Nutritional Immunology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111; and Department of Pathology, Sackler Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111

Aging is associated with reduced IL-2 production and T cell proliferation. Vitamin E supplementation, in aged animals and humans, increases cell division and IL-2 production by naive T cells. The immune synapse forms at the site of contact between a T cell and an APC and participates in T cell activation. We evaluated whether vitamin E affects the redistribution of signaling proteins to the immune synapse. Purified CD4⁺ T cells, from the spleens of young and old mice, were treated with vitamin E before stimulation with a surrogate APC expressing anti-CD3. Using confocal fluorescent microscopy, we observed that CD4⁺ T cells from old mice were significantly less likely to recruit signaling proteins to the immune synapse than cells from young mice. Vitamin E increased the percentage of old CD4⁺ T cells capable of forming an effective immune synapse. Similar results were found following in vivo supplementation with vitamin E. When compared with memory cells, naive T cells from aged mice were more defective in immune synapse formation and were more responsive to vitamin E supplementation. These data show, for the first time, that vitamin E significantly improves age-related early T cell signaling events in naive CD4⁺ T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Institute on Aging Grant R01-AG009140-10A1, Office of Dietary Supplement, the U.S. Department of Agriculture, Agriculture Research Service under Contract Number 58-1950-9-001, a Unilever Health Institute fellowship, and an Ellison Medical Foundation-International Nutrition Foundation fellowship.

² M.G.M. and T.A. had equal contribution to the work presented.

³ Current address: International Centre for Diarrheal Disease Research Immunology Laboratory, Laboratory Sciences Division, G.P.O. Box 128, Dhaka 1000 Bangladesh.

⁴ Address correspondence and reprint requests to Dr. Simin Nikbin Meydani, Nutritional Immunology Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111. E-mail address: simin.meydani{at}tufts.edu

⁵ Abbreviations used in this paper: LAT, linker for activation of T cells; SLP-76, Src homology 2 domain-containing leukocyte protein of 76 kDa; PKC, protein kinase C; PLC, phospholipase C; ROS, reactive oxygen species; PCC, pigeon cytochrome c; ppm, parts per million.

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