Vitamin C treatment of mouse bone marrow-derived dendritic cells enhanced CD8(+) memory T cell production capacity of these cells in vivo

Immunobiology. 2014 Jul;219(7):554-64. doi: 10.1016/j.imbio.2014.03.006. Epub 2014 Mar 20.

Abstract

Vitamin C has been found to stimulate dendritic cells (DCs) to secrete more IL-12 and thereby drive naïve CD4(+) T cells to differentiate into Th1 cells. In the present study, we evaluated the effect of these vitamin C-treated DCs on CD8(+) T cell differentiation both in vitro and in vivo. Mouse bone marrow-derived DCs were prepared in the presence of GM-CSF and IL-15. With vitamin C treatment, these DCs, when LPS-stimulated, secreted more IL-12p70 and IL-15 than did untreated DCs. And when co-cultured with T cells, they yielded a higher frequency of IFN-γ(+) CD8(+) T cells. Moreover, we found that administering vitamin C-treated and tumor lysate-loaded DCs into mice yielded a higher frequency of CD44(high) CD62L(low) CD8(+) effector and effector memory T cells, which showed an increased ex vivo killing effect of the tumor cells. These DCs also elicited enhanced protective effects against inoculated tumor cells, most probably by way of the increased cytotoxic T cells, as was revealed by the decreased growth of the inoculated tumor cells in these mice. This ex vivo vitamin C treatment effect on DCs can be considered as a strategy for boosting DC vaccination potency against tumors.

Keywords: CD8(+) T cells; Dendritic cell vaccination; Dendritic cells; Memory cell differentiation; Vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / immunology*
  • Ascorbic Acid / pharmacology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Flow Cytometry
  • Hyaluronan Receptors / immunology
  • Hyaluronan Receptors / metabolism
  • Immunologic Memory / immunology*
  • Immunotherapy, Adoptive / methods
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism
  • L-Selectin / immunology
  • L-Selectin / metabolism
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy
  • Survival Analysis
  • Vaccination / methods
  • Vitamins / immunology
  • Vitamins / pharmacology

Substances

  • Hyaluronan Receptors
  • Interleukin-15
  • Lipopolysaccharides
  • Vitamins
  • L-Selectin
  • Interleukin-12
  • Interferon-gamma
  • Ascorbic Acid