The broad, long-term objectives of the Massachusetts General Hospital/Harvard Medical School AADCRC entitled "T cell effector and regulatory mechanisms in asthma and food allergy" are to advance the understanding of T cell effector and regulatory mechanisms in allergic diseases. The studies will focus on two allergic conditions relevant to the mission of the agency, namely allergic asthma and food allergy (milk) and utilize clinical models (segmental allergen challenge and oral immunotherapy for food tolerance induction) as a foundation for our basic research studies. The MGH/Harvard AADCRC bench research will explore the balance of T effector and T regulatory activity in asthma and food allergy and the ability of tolerogenic DCs to affect this balance.
Aim #1 of the Human Studies Core is to recruit, enroll and characterize allergic asthmatic and allergic nonasthmatic subjects for the segmental allergen challenge protocol for Project #1, including clinical characterization of the subjects and conducting the segmental allergen challenge procedure and imaging studies. These studies will assess whether allergic asthmatics and allergic nonasthmatics are fundamentally different in terms of T cell effector and T regulatory cell function and also assess whether allergic airway inflammation correlates with physiologic measures such as bronchial hyper-responsiveness and airway physiology utilzing novel and innovative PET-CT imaging techniques.
Aim #2 is to conduct Project #2, a milk oral immunotherapy (OIT) tolerance induction trial, and to collect blood before and following milk tolerance induction to assess T effector and T regulatory cell function and other in vitro measures of allergic sensitization in relation to clinical outcomes of milk OIT.
Aim #3 involves collection of blood and bronchoalveolar lavage samples following segmental allergen challenge and during milk OIT for Project #3, a study of the ability of tolerogenic dendritic cells (DC) to induce T regulatory cells in subjects with allergic asthma and milk allergy. Project #3 is integrated into the segmental allergen challenge protocol and the milk OIT trial to facilitate collection of samples and translation of basic immunologic discovery to clinical allergic conditions. The Human Subjects Core will recruit, enroll and characterize all allergic subjects for SAC and OIT and provide clinical information, spirometry, methacholine bronchial challenge data, blood and BAL samples to the Investigators.

Public Health Relevance

Allergic responses can be viewed as a state in which normal immune tolerance is lacking. It is our hope that our clinical studies involving allergen exposure in subjects with allergic asthma and milk allergy will lead to a better understanding of the role of T effector and T regulatory cells in allergic diseases and the mechanisms involved in lack of tolerance. We also hope our studies will provide novel insights into strategies for restoring immune tolerance, including manipulation of immune-tolerizing dendritic cells (DCs).

National Institute of Health (NIH)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Massachusetts General Hospital
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