Vitamin A deficiency increases the in vivo development of IL-10-positive Th2 cells and decreases development of Th1 cells in mice.
Vitamin A deficiency impairs both T helper type 1 (Th1)- and type 2 (Th2)-mediated immune responses, although Th2 responses seem to be principally affected. Multiple mechanisms are involved in this immune suppression, but the hypothesis that deficiency affects development of Th1/Th2 memory cell phenotype has not been tested directly in vivo. To do so, lymphocytes from DO11.10 T cell receptor (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 (OVA(323-339)). After 2-5 wk, the transferred OVA(323-339)-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 after in vitro stimulation with phorbol myristate acetate and ionomycin. The percentage of CD4(+)KJ1-26(+) cells positive for IL-10 was 100% greater in vitamin A-deficient mice (3.49 +/- 0.41%; mean +/- SE) than in control mice (1.74 +/- 0.37%). IL-4 did not differ between groups. In addition, the percentages of CD4(+)KJ1-26(+) cells from vitamin A-deficient mice that were positive for interferon (IFN)-gamma (8.8 +/- 0.73%) and interleukin (IL)-2 (39.5 +/- 3.1%) were both lower than the percentages 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 T regulatory cells and diminishes the development of Th1 memory cells.
U.S. Department of Agriculture, Western Human Nutrition Research Center at the University of California, Davis, and Nutrition Department, University of California, Davis, CA 95616, USA. cstephensen@ucdavis.edu
Charles B
CB
Stephensen
Xiaowen
X
Jiang
Tammy
T
Freytag
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D010047:Ovalbumin / Q000096:biosynthesis* / Q000276:immunology; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000276:immunology; D011247:Pregnancy; D013388:Succinimides; D018417:Th1 Cells / Q000276:immunology* / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000276:immunology* / Q000378:metabolism
C111390:OVA 323-339; D010446:Peptide Fragments; D013388:Succinimides; D014801:Vitamin A; D016753:Interleukin-10; C037891:3,5-dibromophenylsuccinic acid N-methylimide; D010047:Ovalbumin