In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function.
In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function.
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DOI：
10.4049/jimmunol.152.4.1515
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发表时间：
1994-02
影响因子：
4.4
通讯作者：
M. Cantorna;F. Nashold;C. Hayes
中科院分区：
文献类型：
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作者：
M. Cantorna;F. Nashold;C. Hayes
在维生素 A 缺乏症中，Ab 介导的免疫力严重受损。我们报道，旋毛虫感染在对照小鼠中刺激了强烈的 Th2 细胞反应，但在维生素 A 缺乏的小鼠中，它刺激了强烈的 Th1 细胞反应。在这里，我们研究了从 Th2 主导反应转变为 Th1 主导反应的免疫生物学机制。动力学分析显示，在缺陷小鼠中，Th1 细胞首先发育，并且主要分泌 IFN-γ，而在对照小鼠中，Th2 细胞发育较晚，并且主要分泌 IL-5 和 IL-10。分泌 IFN-γ 的细胞频率相同，但缺陷小鼠的细胞分泌 IFN-γ 的速度比对照小鼠的细胞快六倍，并且体外添加视黄酸使该速度降低了 50%。相比之下，缺陷小鼠的IL-5分泌率相同，但IL-5分泌细胞频率低于对照组，并且体外添加视黄酸使该频率加倍，而与其对IFN-γ的抑制作用无关。来自缺陷小鼠的 APC 比对照 APC 刺激更多的 IFN-γ 释放，并且体外添加视黄酸使该活性降低 50%。这些结果共同确定了至少三种维生素 A 活性，可平衡 Th1 和 Th2 功能、直接下调 Th1 细胞 IFN-γ 分泌、降低激活的 APC 功能以及促进 Th2 细胞生长和/或分化。在这个系统和其他系统中，调节性 Th1 和 Th2 细胞之间的不平衡是维生素 A 缺乏症中 Ab 介导的免疫不良的一种机制。
In hypovitaminosis A, Ab-mediated immunity is severely impaired. We reported that Trichinella spiralis infection stimulates a strong Th2 cell response in control mice but in vitamin A-deficient mice it stimulates a strong Th1 cell response. Here we investigated the immunobiologic mechanisms underlying this shift from a Th2- to a Th1-dominated response. A kinetic analysis showed that the Th1 cells developed first and IFN-gamma secretion predominated in deficient mice, whereas the Th2 cells developed later and IL-5 and IL-10 secretion predominated in control mice. The IFN-gamma-secreting cell frequencies were the same but cells from deficient mice secreted IFN-gamma sixfold faster than cells from control mice, and retinoic acid addition in vitro decreased that rate 50%. In contrast, the IL-5-secretion rates were the same but the IL-5-secreting cell frequency was lower in deficient mice than in controls, and retinoic acid addition in vitro doubled this frequency independently of its inhibitory effect on IFN-gamma. The APC from deficient mice stimulated greater IFN-gamma release than control APC and retinoic acid addition in vitro decreased this activity 50%. Together these results identify at least three vitamin A activities that balance Th1 and Th2 functions, down-regulating Th1 cell IFN-gamma secretion directly, decreasing activated APC function, and promoting Th2 cell growth and/or differentiation. In this system and perhaps others, the imbalance between regulatory Th1 and Th2 cells is one mechanism underlying poor Ab-mediated immunity in hypovitaminosis A.