VITAMIN-A-DEFICIENCY RESULTS IN A PRIMING ENVIRONMENT CONDUCIVE FOR TH1 CELL-DEVELOPMENT
VITAMIN-A-DEFICIENCY RESULTS IN A PRIMING ENVIRONMENT CONDUCIVE FOR TH1 CELL-DEVELOPMENT
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DOI：
10.1002/eji.1830250629
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发表时间：
1995-06-01
影响因子：
5.4
通讯作者：
HAYES, CE
中科院分区：
文献类型：
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作者：
CANTORNA, MT;NASHOLD, FE;HAYES, CE
某些感染，如人类免疫缺陷病毒-1，会消耗维生素A，当维生素A水平低时，免疫功能障碍会导致进一步感染的易感性。我们的研究主要集中在维生素a缺乏导致的免疫功能障碍和进一步感染的易感性。我们之前对蠕虫感染小鼠的研究表明，当维生素a水平较低时，免疫反应发生强烈的调节性T细胞失衡，T辅助1型细胞干扰素(IFN)- γ合成过多，T辅助2型细胞发育和功能不足。在这里，我们研究了维生素a缺乏小鼠的T细胞启动环境，以了解启动环境如何产生调节性T细胞失衡，从而扭曲免疫系统对感染的反应能力。我们的研究结果表明，在维生素A缺乏期间，启动环境包括组成性白介素(IL)-12和ifn - γ转录本，但缺乏组成性IL-4和IL-10转录本。饲粮中添加全黄酮维甲酸可下调构成性IL-12和ifn - γ转录本的水平。此外，当来自幼稚的维生素a缺乏动物的T细胞通过T细胞受体受到刺激时，与来自对照动物的T细胞相比，它们产生了更多的ifn - γ蛋白。相比之下，T细胞刺激不能诱导IL-4或IL-10分泌。诱导的ifn - γ主要来自CD8(+) T细胞，体外添加全反式维甲酸在转录水平上抑制ifn - γ的产生。体外添加维甲酸也在转录物水平上降低了自然杀伤细胞ifn - γ的合成。综上所述，当维生素A水平较低时，扭曲的组成型和诱导型细胞因子基因表达模式将强烈地促进T辅助型1的发育，限制T辅助型2细胞的生长和分化，从而限制动物的体液免疫反应能力。
Certain infections, like that with the human immunodeficiency virus-1, deplete vitamin A, and when vitamin A levels are low, immune dysfunctions establish susceptibility to further infection. Our research has focused on the immune dysfunctions that are a consequence of vitamin A deficiency and that predispose to further infection. We previously studied a helminth infection in mice, and showed that when vitamin A levels are low, the immune response develops a strong regulatory T cell imbalance with excessive T helper type-1 cell interferon (IFN)-gamma synthesis and insufficient T helper type-2 cell development and function. Here, we studied the T cell priming environment in vitamin A-deficient mice to learn how that priming environment might produce a regulatory T cell imbalance and consequently distort the ability of the immune system to respond to an infection. Our results show that during vitamin A deficiency, the priming environment included constitutive interleukin (IL)-12 and IFN-gamma transcripts, but it was devoid of constitutive IL-4 and IL-10 transcripts. Dietary all-tuans-retinoic acid supplementation down-regulated the level of constitutive IL-12 and IFN-gamma transcripts. Furthermore, when T cells from naive vitamin A-deficient animals were stimulated through the T cell receptor, they produced excess IFN-gamma protein compared to T cells from control animals. In contrast, T cell stimulation failed to induce IL-4 or IL-10 secretion. The inducible IFN-gamma was largely from CD8(+) T cells and all-trans-retinoic acid addition in vitro inhibited IFN-gamma production at the transcript level. Retinoic acid addition in vitro also decreased natural killer cell IFN-gamma synthesis at the transcript level. Taken together, the distorted constitutive and inducible cytokine gene expression patterns that occurred when vitamin A levels were low would be expected strongly to favor T helper type-1 development and limit T helper type-2 cell growth and differentiation, thereby limiting the animal's humoral immune response capability.