IL-4 and IL-10 are both required for the induction of oral tolerance.
IL-4 and IL-10 are both required for the induction of oral tolerance.
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DOI：
10.4049/jimmunol.162.5.2613
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发表时间：
1999-03
影响因子：
4.4
通讯作者：
L. Rizzo;R. Morawetz;N. Miller-Rivero;R. Choi;B. Wiggert;C. Chan;H. Morse;R. Nussenblatt;R. Caspi
中科院分区：
文献类型：
--
作者：
L. Rizzo;R. Morawetz;N. Miller-Rivero;R. Choi;B. Wiggert;C. Chan;H. Morse;R. Nussenblatt;R. Caspi
实验性自身免疫性葡萄膜炎（EAU）的发展可以通过在用相同蛋白质进行葡萄膜激发之前喂饲小鼠光感受器间类维生素A结合蛋白来诱导保护。两种不同的方案在诱导保护性耐受方面同样有效，尽管它们似乎是通过不同的机制实现的：一种涉及调节性细胞因子（IL-4、IL-10和TGF-β），另一种涉及细胞因子的最小参与。在这里，我们研究了IL-4和IL-10对口服耐受性发展的重要性，使用基因工程小鼠缺乏这些细胞因子中的一种或两种。在这些动物中，我们只能通过诱导非依赖于尼古丁的耐受性的方案来保护EAU。当这些动物被喂食野生型动物中被认为主要诱导调节细胞并与细胞因子分泌相关的方案时，它们没有受到EAU的保护。有趣的是，这两种方案都与减少IL-2的产生和增殖的感光细胞间类维生素A结合蛋白。这些发现表明，IL-4和IL-10都是诱导依赖于调节细胞因子的保护性口服耐受所必需的，并且在此过程中一种细胞因子不能替代另一种细胞因子。这些数据还强调了这样一个事实，即口服耐受性，表现为抑制增殖和IL-2的产生，并不等同于保护免受疾病。
Protection from the development of experimental autoimmune uveitis (EAU) can be induced by feeding mice interphotoreceptor retinoid binding protein before uveitogenic challenge with the same protein. Two different regimens are equally effective in inducing protective tolerance, although they seem to do so through different mechanisms: one involving regulatory cytokines (IL-4, IL-10, and TGF-beta), and the other with minimal involvement of cytokines. Here we studied the importance of IL-4 and IL-10 for the development of oral tolerance using mice genetically engineered to lack either one or both of these cytokines. In these animals we were able to protect against EAU only through the regimen inducing cytokine-independent tolerance. When these animals were fed a regimen that in the wild-type animal is thought to predominantly induce regulatory cells and is associated with cytokine secretion, they were not protected from EAU. Interestingly, both regimens were associated with reduced IL-2 production and proliferation in response to interphotoreceptor retinoid binding protein. These findings indicate that both IL-4 and IL-10 are required for induction of protective oral tolerance dependent on regulatory cytokines, and that one cytokine cannot substitute for the other in this process. These data also underscore the fact that oral tolerance, manifested as suppression of proliferation and IL-2 production, is not synonymous with protection from disease.