Vitamin C enters mouse T cells as dehydroascorbic acid in vitro and does not recapitulate in vivo vitamin C effects

Hyung Gun Maeng, Hyunja Lim, Young joo Jeong, Ami Woo, Jae Seung Kang, Wang Jae Lee, Young il Hwang

Research output: Contribution to journalArticle

19 Citations (Scopus)

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-γ, TNF-α, 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.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalImmunobiology
Volume214
Issue number4
DOIs
StatePublished - 1 Apr 2009

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Dehydroascorbic Acid
Ascorbic Acid
T-Lymphocytes
Facilitative Glucose Transport Proteins
Cytokines
In Vitro Techniques
Biological Phenomena
Ionomycin
Micronutrients

Keywords

  • Ascorbic acid
  • Dehydroascorbic acid
  • GLUT
  • Mouse T cell
  • Vitamin C

Cite this

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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-γ, TNF-α, 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.",
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Vitamin C enters mouse T cells as dehydroascorbic acid in vitro and does not recapitulate in vivo vitamin C effects. / Maeng, Hyung Gun; Lim, Hyunja; Jeong, Young joo; Woo, Ami; Kang, Jae Seung; Lee, Wang Jae; Hwang, Young il.

In: Immunobiology, Vol. 214, No. 4, 01.04.2009, p. 311-320.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Vitamin C enters mouse T cells as dehydroascorbic acid in vitro and does not recapitulate in vivo vitamin C effects

AU - Maeng, Hyung Gun

AU - Lim, Hyunja

AU - Jeong, Young joo

AU - Woo, Ami

AU - Kang, Jae Seung

AU - Lee, Wang Jae

AU - Hwang, Young il

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AB - 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-γ, TNF-α, 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.

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