Mechanisms of Clinical Reactivity or Tolerance to Mouse Allergen

描述（由研究者提供）：尽管对过敏性免疫反应的发病机制进行了大量的研究，但对天然过敏原暴露如何影响随后的过敏原特异性免疫反应，以及特应性处置是否改变过敏原暴露-免疫反应关系的了解甚少。在拟议的研究中，过敏原暴露的职业模型将被用来测试一个总体假设，即自然暴露于小鼠过敏原的水平会影响随后对小鼠主要过敏原Mus m1的免疫反应，并最终影响临床过敏表型。为了验证这些假设，我们将继续跟踪Jackson实验室（TJL）的工作人员，他们目前正在参加一项前瞻性队列研究，即jax队列研究，并招募更多的新工作人员加入队列。具体目的如下：(1)继续反复评估小鼠过敏原暴露、小鼠过敏原特异性体液反应以及当前和新入组参与者的临床过敏表型；(2)评估当前和新入组受试者中IgG、IgG4和IgE小鼠过敏原表位谱的多样性；(3)评估新入组参与者小鼠特异性Tr1细胞频率；(4)通过评估新ige致敏队列成员的嗜碱性粒细胞表型和抗原提呈细胞对Mus m1的摄取来评估ige介导的功能。我们将研究过敏原暴露水平与这些过敏原特异性免疫反应和临床过敏表型之间的关系。在重复评估个人过敏原暴露是可行的情况下，提出的前瞻性队列研究可以说是理解这些复杂的、时间和暴露依赖关系的最佳方法。本研究结果将有助于更好地了解过敏原暴露和免疫反应的自然历史，为预防和治疗过敏性疾病的免疫调节策略的发展提供基础。

DESCRIPTION (provided by investigator): Although there has been a great deal of investigation into the pathogenesis of the allergic immune response, there is very little understanding of how natural allergen exposure influences the ensuing allergen-specific immune responses, and whether atopic disposition modifies allergen exposure-immune response relationships. In the proposed study, an occupational model of allergen exposure will be used to test the overarching hypothesis that the level of natural exposure to mouse allergen influences the subsequent immune responses to the major mouse allergen, Mus m 1, and ultimately, the clinical allergy phenotype. To test these hypotheses, we will continue to follow workers at The Jackson Laboratory (TJL) who are currently enrolled in a prospective cohort study, the JAXCohort Study, and recruit additional new workers into the cohort. The specific aims are as follows: (1) To continue to repeatedly assess mouse allergen exposure, mouse allergen-specific humoral responses, and clinical allergy phenotype in currently and newly enrolled participants; (2) To assess the diversity of IgG, IgG4, and IgE mouse allergen epitope repertoires among current and newly enrolled participants; (3) To assess mouse-specific Tr1 cell frequency in newly enrolled participants; and (4) To assess IgE-mediated function by assessing basophil phenotypes and Mus m 1 uptake by antigen presenting cells in newly IgE-sensitized cohort members. We will examine relationships between allergen exposure levels and these allergen-specific immune responses and clinical allergy phenotype. The proposed prospective cohort study, in a setting in which repeated assessments of personal allergen exposure are feasible, is arguably the best approach to understanding these complex, time- and exposure-dependent relationships. Findings from this study will result in a better understanding of the natural history of allergen exposure and immune responses that will provide a foundation for the development of immunomodulatory strategies aimed at prevention and treatment of allergic diseases. PUBLIC HEALTH RELEVANCE: A more detailed understanding of the relationship between allergen exposure and disease is needed to develop better preventive and treatment strategies. We will take advantage of the ability to study dose-response relationships more precisely in an occupational setting as a model to address this relationship. We will compare aspects of our findings in these workers to people with mouse allergy living with high levels of allergen in inner city Baltimore in the hope that the knowledge gained from this study will provide the foundation upon which to devise preventive and therapeutic interventions in occupational and community settings.