Stephensen Charles B, Jiang Xiaowen, Freytag Tammy
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.
J Nutr. 2004 Oct;134(10):2660-6. doi: 10.1093/jn/134.10.2660.
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.
维生素A缺乏会损害1型辅助性T细胞（Th1）和2型辅助性T细胞（Th2）介导的免疫反应，不过Th2反应似乎受到的影响最为主要。这种免疫抑制涉及多种机制，但维生素A缺乏影响Th1/Th2记忆细胞表型发育的假说尚未在体内进行直接验证。为此，将来自DO11.10 T细胞受体（TCR）转基因小鼠的淋巴细胞转移至维生素A缺乏或对照BALB/c受体小鼠体内。然后用针对TCR转基因DO11.10 T细胞的同源肽抗原（OVA(323 - 339)）对受体小鼠进行免疫。2 - 5周后，用TCR克隆型抗体KJ1 - 26从引流淋巴结中鉴定出转移的OVA(323 - 339)特异性T细胞，并用佛波酯肉豆蔻酸酯乙酸盐和离子霉素进行体外刺激后，通过细胞内细胞因子染色来确定其Th1/Th2表型。维生素A缺乏小鼠中白细胞介素10（IL - 10）阳性的CD4(+)KJ1 - 26(+)细胞百分比（3.49±0.41%；平均值±标准误）比对照小鼠（1.74±0.37%）高100%。两组间白细胞介素4（IL - 4）无差异。此外，维生素A缺乏小鼠中干扰素γ（IFN - γ）阳性（8.8±0.73%）和白细胞介素2（IL - 2）阳性（39.5±3.1%）的CD4(+)KJ1 - 26(+)细胞百分比均低于对照小鼠（分别为11.4±0.67和47.0±2.8%）。因此，在初次接触抗原时，维生素A缺乏会促进产生IL - 10的Th2或调节性T细胞的发育，并减少Th1记忆细胞的发育。
