title: Vitamin C promotes maturation of T-cells.
abstract: OBJECTIVE
  Vitamin C (ascorbic acid) is thought to enhance immune function, but the mechanisms involved are obscure. We utilized an in vitro model of T-cell maturation to evaluate the role of ascorbic acid in lymphocyte development.
  
  
  RESULTS
  Ascorbic acid was essential for the developmental progression of mouse bone marrow-derived progenitor cells to functional T-lymphocytes in vitro and also played a role in vivo. Ascorbate-mediated enhancement of T-cell development was lymphoid cell-intrinsic and independent of T-cell receptor (TCR) rearrangement. Analysis of TCR rearrangements demonstrated that ascorbic acid enhanced the selection of functional TCRαβ after the stage of β-selection. Genes encoding the coreceptor CD8 as well as the kinase ZAP70 were upregulated by ascorbic acid. Pharmacologic inhibition of methylation marks on DNA and histones enhanced ascorbate-mediated differentiation, suggesting an epigenetic mechanism of Cd8 gene regulation via active demethylation by ascorbate-dependent Fe(2+) and 2-oxoglutarate-dependent dioxygenases.
  
  
  METHODS
  We speculate that one aspect of gene regulation mediated by ascorbate occurs at the level of chromatin demethylation, mediated by Jumonji C (JmjC) domain enzymes that are known to be reliant upon ascorbate as a cofactor. JmjC domain enzymes are also known to regulate transcription factor activity. These two mechanisms are likely to play key roles in the modulation of immune development and function by ascorbic acid.
  
  
  CONCLUSIONS
  Our results provide strong experimental evidence supporting a role for ascorbic acid in T-cell maturation as well as insight into the mechanism of ascorbate-mediated enhancement of immune function.
authors.affiliation: 1 Division of Hematology, Department of Medicine, University of Utah , Salt Lake City, Utah.
authors.forename: Jared
authors.initials: J
authors.lastname: Manning
authors.forename: Birgitta
authors.initials: B
authors.lastname: Mitchell
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Appadurai
authors.forename: Arvind
authors.initials: A
authors.lastname: Shakya
authors.forename: Laura Jean
authors.initials: LJ
authors.lastname: Pierce
authors.forename: Hongfang
authors.initials: H
authors.lastname: Wang
authors.forename: Vincent
authors.initials: V
authors.lastname: Nganga
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
authors.forename: James M
authors.initials: JM
authors.lastname: May
authors.forename: Dean
authors.initials: D
authors.lastname: Tantin
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Spangrude
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D044127:Epigenesis, Genetic / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D015329:Gene Rearrangement, T-Lymphocyte / Q000187:drug effects; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D010797:Phthalimides / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011799:Quinazolines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001381:Azepines; C518299:BIX 01294; D003470:Culture Media; D006657:Histones; D007155:Immunologic Factors; D010797:Phthalimides; D011799:Quinazolines; C503639:RG108; D011948:Receptors, Antigen, T-Cell; D014364:Tryptophan; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D001205:Ascorbic Acid