Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2004
Publication Date: 7/7/2004
Citation: Stephensen, C.B., Jiang, X., Freytab, T. 2004. Vitamin a deficiency increases increases in vivo development of il-10-prositive th2 cells and decreases development of th-1 cells in mice. Journal of Nutrition. 134:2660-2666, 2004.
Interpretive Summary: The goal of this study was to determine if vitamin A deficiency affected the development of type 1 or type 2 memory cells in mice. We used a T-cell receptor transgenic mouse system in order to directly examine the effect of vitamin A deficiency on naive T cells that we can identify with a specific antibody that respond to a known antigen. We found that vitamin A deficiency increased the frequency of interleukin-10 (IL-10)producing cells by 2-fold. Since IL-10 is a regulatory cytokine that helps to down-regulate active immune responses, this observation may help explain how vitamin A deficiency impairs certain aspects of immune function.
Technical Abstract: Vitamin A deficiency impairs both Th1- and Th2-mediated immune responses. Th2 responses seem to be particularly depressed. Although multiple mechanisms may be involved, these observations suggest that vitamin A deficiency may decrease development of Th2 memory cells. This hypothesis has not been directly tested in vivo. To do so, lymphocytes from DO11.10 TCR-transgenic mice were transferred to vitamin A-deficient or control BALB/c recipients. Recipients were then immunized with the cognate peptide antigen for the TCR-transgenic DO11.10 T-cells (OVA323-339). Two to five weeks later the transferred OVA323-339-specific T-cells were identified from draining lymph nodes with the TCR-clonotypic antibody KJ1-26 and their Th1/Th2 phenotype was characterized by intracellular cytokine staining following in vitro stimulation with phorbol myristate acetate and ionomycin. The percentage of CD4+KJ1-26+ cells positive for IL-10 was two-fold greater in vitamin A-deficient mice (3.49 " 0.41%; mean " standard error) than in control mice (1.74 " 0.37%). No difference was seen for IL-4. In addition, the percentages of CD4+KJ1-26+ cells from vitamin A-deficient mice that were positive for IFN-( (8.8 " 0.73%) and IL-2 (39.5 " 3.1%) were both lower than the percentages seen in control mice (11.4 " 0.67% and 47.0 " 2.8%, respectively). Thus vitamin A deficiency at the time of initial antigen exposure enhances the development of IL-10-producing Th2 or Treg cells and diminishes the development of Th1 memory cells.