title: Vitamin C enters mouse T cells as dehydroascorbic acid in vitro and does not recapitulate in vivo vitamin C effects.
abstract: Vitamin C is an essential micronutrient, which has been implicated in various biological processes, including immune response. In fact, in vivo administration of vitamin C modulates T cell proliferation and cytokine secretion. In this study, we analyzed the mechanism by which mouse T cells take up vitamin C, and whether this uptake directly affected T cell functions. T cells internalized more vitamin C when they were activated, due to enhanced glucose transporter (GLUT)-1 and GLUT-3 expression that persisted up to 48 h after activation. Blocking oxidation of ascorbic acid (the reduced form of vitamin C) in the culture medium with 1,4-dithio-threitol (DTT) almost completely inhibited the enhanced vitamin C uptake. The presence of vitamin C at low concentrations during in vitro T cell activation did not affect proliferation or cytokine secretion (IFN-gamma, TNF-alpha, or IL-4) in response to PMA/ionomycin. In contrast, high concentrations (0.25-0.5 mM) of vitamin C lowered cell viability, reduced thymidine uptake, and decreased cytokine secretion. In conclusion, activated T cells upregulated GLUT-1 and -3 to increase vitamin C uptake. They took up vitamin C mostly in its oxidized form, rarely in its reduced form. Application of vitamin C to T cells in vitro did not recapitulate previously reported in vivo responses to vitamin C, suggesting that in vivo, vitamin C modulates T cells indirectly through other components of the microenvironment.
authors.affiliation: Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea.
authors.forename: Hyung Gun
authors.initials: HG
authors.lastname: Maeng
authors.forename: Hyunja
authors.initials: H
authors.lastname: Lim
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Ami
authors.initials: A
authors.lastname: Woo
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang