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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #201748
Title: Age and vitamin E-induced changes in Gene Expression Profiles of T cells

Author
item HAN, SUNG NIM - TUFTS/HNCRA
item ADOLFSSON, OSKAR - NESTLE RESEARCH CENTER
item LEE, CHEOL-KOO - KOREA UNIV, SEOUL
item PROLLA, TOMAS - UNIV WISCONSIN, MADISON
item Ordovas, Jose
item Meydani, Simin

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/16/2006
Publication Date: 12/1/2006
Citation: Han, S., Adolfsson, O., Lee, C., Prolla, T.A., Ordovas, J.M., Meydani, S. 2006. Age and vitamin E-induced changes in Gene Expression Profiles of T cells. Journal of Immunology. 177(12): 6052-6061.

Interpretive Summary: Aging is associated with defective function of immune response, which is believed to contribute to the higher incidence of illness and death from infectious diseases and cancers. Among the immune cells, T cells are the most vulnerable to age-associated disfunction. Although several investigators have conducted studies to determine the cause of age-related defects in T cell function, there is no complete understanding of the changes that lead to T cell malfunction. Vitamin E has been shown to enhance T cell-mediated functions in aged animals and humans. In the current study, we investigated the gene expression profiles of T cells from young and old mice to address which genes or group of genes in resting as well as activated T cells are affected by aging and vitamin E supplementation. We identified several groups of genes, which are influenced by aging and which could explain the lower ability of T cells to multiply as needed and their tendency toward cell death. Vitamin E supplementation in animals and human subjects resulted in increased immune response and decreased production of chemical substances that suppress the immune system. We also observed age- and vitamin E-induced changes in several genes, which have not been previously reported, but might be of significant relevance to age- and vitamin E induced changes in T cell functions. While further studies are needed to clarify the specific mechanisms by which vitamin E specifically enhances T cell function in the aged, nevertheless, these studies contribute to advancing our understanding of the age-related disfunction of the immune system in order to learn how to strengthen this system in the aged regarding preventive health care as well as intervention during illness.

Technical Abstract: T cell is vulnerable to age associated changes and vitamin E has been shown to improve T cell functions in the old. We studied the gene expression profile of T cells to better understand the underlying mechanisms of age and vitamin E-induced changes in T cell function. Young and old C57BL mice were fed diets containing 30 ppm (control) or 500 ppm (E) of vitamin E for 4 wks. Gene expression profile of purified T cells was assessed in presence or absence of anti-CD3 and anti-CD28 using microarray analysis. Genes associated with cytokines and chemokines, regulation of transcription, signal transduction, cell cycle and apoptosis were significantly up-regulated upon stimulation. Responsiveness of T cells to stimulation was influenced by age in 40 genes and by vitamin E in 21 genes. Among those genes, higher expression of SOCS3 and lower expression of Gfi1 in old may contribute to the age-associated decline in proliferation, while higher expression of Gadd45 and lower expression of Bcl2 may contribute to the increased apoptosis observed in old T cells. Vitamin E supplementation resulted in higher expression of many genes involved in cell cycle regulation (Ccnb2, Cdc2, Cdc6) and nucleic acid metabolism in both un-stimulated and stimulated T cells from old mice. Following stimulation, T cells from both young and old mice supplemented with vitamin E had higher up-regulation of IL-2 expression while old T cells from vitamin E-supplemented mice exhibited lower upregulation of IL-4 expression compared to those of control mice. These findings suggest that: 1) aging has significant effects on the expression of genes associated with signal transduction, transcriptional regulation, and apoptosis pathways in T cells, and 2) vitamin E has a significant impact on the expression of genes associated with cell cycle and Th1/Th2 balance in old T cells.