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Unconventional T cell activities in young animals

幼年动物的非常规 T 细胞活性

基本信息

批准号：
7013611
负责人：
ADRIAN Clive HAYDAY
金额：
$ 23.73万
依托单位：
KING'S COLLEGE LONDON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2007-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7013611
关键词：
Coccidia T lymphocyte asthma clinical research cord blood developmental immunology food hypersensitivity genetically modified animals human fetus tissue immune response immunoregulation interferon gamma juvenile animal laboratory mouse leukocyte activation /transformation ovalbumin parasitic gastrointestinal disorder peanuts

项目摘要

DESCRIPTION (provided by applicant): There is a strong body of evidence that the sensitivity to allergies, such as asthma, results from a dysregulation of immune responses in early life. This obliges us to better understand early life immune responses, and in particular, the expression of interferon gamma (IFN gamma), a cytokine with the capacity to down-regulate allergic T cell responses. We have recently shown that in early life, unconventional T cells, in particular gamma delta cells, are an important source of IFN gamma, and that young mice depend on such cells for primary protection against mucosal infection. Therefore, it is logical to ask whether the experimental up-regulation of unconventional T cells in early life will promote IFN gamma production that will alter the susceptibility to allergy. To accomplish this, mice will be infected with a natural gut pathogen that activates gamma delta cells, and their susceptibility then assessed to food allergy, and to airway hypersensitivity. The gut, rather than the lung, has been chosen as the primary target of unconventional T cell activation because the appropriate natural infection system is in place. In short, the first aim of the application is a proof of principle. Nevertheless, should the protocol successfully regulate allergy, it will lay an important foundation to attempt to regulate unconventional T cells directly in the lung (which is beyond the scope of this application) or to use non-infectious protocols to regulate unconventional T cells more globally, which is the subject of Aims 2 and 3. Although the immune systems of young mice and human children differ in their states of maturity, data are presented that show the relevance of human gamma delta cells to the production of IFN gamma in early life. Thus, Aim 4 will examine the degree to which the strategies that we develop in the animal model may be practically applied to humans.

描述（由申请人提供）：有强有力的证据表明，对过敏的敏感性，如哮喘，是由早期免疫反应失调引起的。这使我们能够更好地理解生命早期的免疫反应，特别是干扰素γ (IFN γ)的表达，干扰素γ是一种具有下调过敏性T细胞反应能力的细胞因子。我们最近的研究表明，在生命早期，非常规T细胞，特别是γ δ细胞，是IFN γ的重要来源，并且年轻的小鼠依赖于这些细胞作为抵抗粘膜感染的初级保护。因此，我们有必要问，在生命早期非常规T细胞的实验性上调是否会促进IFN γ的产生，从而改变对过敏的易感性。为了实现这一目标，将小鼠感染一种激活γ δ细胞的天然肠道病原体，然后评估它们对食物过敏和气道过敏的易感性。肠道，而不是肺，已经被选为非常规T细胞激活的主要目标，因为合适的自然感染系统已经到位。简而言之，应用程序的第一个目的是证明原理。然而，如果该方案成功调节过敏，将为尝试直接调节肺中的非常规T细胞（超出本应用范围）或使用非感染性方案更全面地调节非常规T细胞奠定重要基础，这是Aims 2和3的主题。尽管幼鼠和人类儿童的免疫系统在成熟状态上有所不同，但已有数据表明，人类γ δ细胞与生命早期IFN γ的产生有关。因此，Aim 4将检查我们在动物模型中开发的策略可能实际应用于人类的程度。