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Nutritional Immunology

Vitamin A Deficiency Increases the In Vivo Development of IL-10–Positive Th2 Cells and Decreases Development of Th1 Cells in Mice^1,2

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

³To whom correspondence should be addressed. E-mail: cstephensen{at}ucdavis.edu.

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)- (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.

KEY WORDS: • rodent • Th1/Th2 • immunomodulators • transgenic/knockout • vitamin A deficiency

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