Age-associated decline in effective immune synapse formation of CD4+ T cells is reversed by vitamin E supplementation

Authors: MARKO, MELISSA - HNRCA AT TUFTS; AHMED, TANVIR - HNRCA AT TUFTS; BUNNELL, STEPHEN - TUFTS SCHOOL OF MEDICINE; WU, DAYONG - HNRCA AT TUFTS; CHUNG, HEEKYUNG - HNRCA AT TUFTS; HUBER, BRIGITTE - TUFTS SCHOOL OF MEDICINE; Meydani, Simin

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/18/2006
Publication Date: 1/15/2007
Citation: Marko, M.G., Ahmed, T., Bunnell, S.C., Wu, D., Chung, H., Huber, B.T., Meydani, S. 2007. Age-associated decline in effective immune synapse formation of CD4+ T cells is reversed by vitamin E supplementation. Journal of Immunology. 178:1443-1449.

Interpretive Summary: Aging is associated with reduced immune function, particularly T cell function. Supplementation with vitamin E in aged animals and humans increases T cell function. The purpose of these experiments was to determine how vitamin E specifically enhances aging T cells and their ability to function normally. T cells cannot directly recognize an antigen, which is a potentially harmful organism. An antigen needs to be taken up or "devoured", processed for information about it, and then presented to the T cells by a group of cells called antigen-presenting cells (APC). When APC present antigens to T cells, a juncture is formed between the two types of cells. This structure is called an immune synapse and its function is to deliver the signal to T cells to activate them against the specific organism (antigen). We evaluated whether vitamin E positively affects the function of signaling proteins, which are the molecules that transmit the signal. Purified CD4+ T cells, from the spleens of young and old mice, were treated with vitamin E before being stimulated with the corresponding APC. Using confocal fluorescent microscope, 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 dietary supplementation with vitamin E. These data show, for the first time, that vitamin E significantly improves age-related early T cell signaling events in CD4+ T cells resulting in improved age-specific immune function. This finding will make it easier to understand the reason T cell function deteriorates as humans age and allow us to learn ways to use nutrition and supplementation to improve the function of the immune system.

Technical Abstract: 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 naïve T cells. The immune synapse forms at the site of contact between a T cell and an antigen-presenting cell (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 to memory cells, naïve 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 naïve CD4+ T cells.