ALTERED RESPONSES TO FOOD PROTEINS IN ENTERIC INFECTION

口服可溶性蛋白抗原通常会导致 抗原特异性全身性无反应。然而，公安局发现， 当一种模型食物蛋白，卵清蛋白(OVA)被口服给小鼠时 感染了线虫寄生虫(多回螺旋线虫)，这通常是 全身OVA特异性Th2反应的耐受性刺激素数。我们有 研究表明，由此诱导的极化Th2细胞因子反应 肠道感染是决定是否耐受的核心因素。 对OVA有诱导作用。我们还发现，多回血吸虫感染有可能 促进T细胞克隆性增殖和增强对口服抗原的应答 上调共刺激分子在黏膜抗原提呈上的表达 细胞(APC)。在具体目标1中，我们将进一步探讨 通过检查感染对各种APC的影响来解释这一效应的基础 能在粘膜和胃粘膜中呈递口服抗原的种群 周围淋巴组织。检查蠕虫感染的方式 改变OVA特异性T细胞反应，来自OVA特异性TCR的T细胞 转基因小鼠将适应性地转移到正常BALB/c小鼠和 他们的反应将在体内进行跟踪。除了提供对以下方面的见解 一种感染使反应偏向于其他抗原的能力，这些 实验将提供有关抗原呈递的基本信息 粘膜免疫系统及其协调决策的方式 关于宽容和豁免权。因为寄生虫感染在许多地方都是地方病 在第三世界的部分地区，我们的观察具有重要的临床意义 这意味着什么。Th2偏向感染偏离免疫功能的能力 对其他抗原的反应也有很好的文献记载。我们的模型扩展了这些 一个新方向的发现表明，肠道感染可以引起 对一种正常耐受性抗原的偏向Th2的免疫反应。这 提示蠕虫感染可能是过敏现象的先兆，并可能 影响口服疫苗的反应。在具体目标2中，我们将因此 检查蠕虫感染引发过敏反应的能力 一种食物抗原，并探索这些发现与临床食物的相关性 过敏。我们还将研究粘膜寄生虫的实际意义。 用于口服疫苗接种的感染。如果蠕虫感染偏向Th2应答 到了口服疫苗接种阶段，成功开展了口服疫苗接种运动 国家可能取决于控制这些感染的能力来改变 对疫苗抗原的反应。粘膜影响的表征 使用该小鼠模型口服疫苗后的感染反应可能 建议最大限度地提高口服疫苗的预期反应的方法。

Oral administration of soluble protein antigens typically induces antigen specific systemic nonresponsiveness. However, the PI has found that when a model food protein, ovalbumin (OVA), is orally administered to mice infected with a nematode parasite (Heligmosomoides polygyrus), this normally tolerogenic stimulus primes for a systemic OVA specific Th2 response. We have shown that the polarized Th2 cytokine response induced by this enteric infection plays a central role in determining whether or not tolerance to OVA is induced. We have also found that H. polygyrus infection potentates the response to oral antigen by enhancing T cell clonal expansion and upregulating costimulatory molecule expression on mucosal antigen presenting cells (APC). In Specific Aim 1,we will further explore the mechanistic basis for this effect by examining the influence of infection on various APC populations which can present orally administered antigens in mucosal and peripheral lymphoid tissue. To examine the ways in which helminth infection alters the OVA specific T cell response, T cells from OVA specific TCR transgenic mice will be adaptively transferred into normal BALB/c mice and their response will be tracked in vivo. In addition to providing insight into the ability of an infection to bias the response to other antigens, these experiments will provide basic information on antigen presentation in the mucosal immune system and the means by which it orchestrates decisions concerning tolerance and immunity. Since parasitic infection is endemic in many parts of the Third World, our observations have important clinical implications. The ability of Th2 biased infections to deviate the immune response to other antigens is well documented. Our model extends these findings in a novel direction by showing that enteric infection can elicit a Th2-biased immune response to a normally tolerogenic form of antigen. This suggests that helminth infection may pre-dispose for allergic phenomena and may affect the response to oral vaccines. In Specific Aim 2, we will therefore examine the ability of helminth infection to prime for an allergic response to a food antigen and explore the relevance of these findings to clinical food allergy. We will also examine the practical implications of mucosal parasitic infection for oral vaccination. If helminth infection biases for a Th2 response to oral vaccination, the success of oral vaccination campaigns in developing countries may hinge upon controlling the ability of these infections to alter responses to vaccine antigens. Characterization of the influence of mucosal infection on the response to oral vaccination using this murine model may suggest methods for maximizing the desired response to oral vaccines.