PULMONARY IMMUNE RESPONSE TO INHALED PARTICULATES

Massachusetts General Hospital, Boston MA

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Abstract

DESCRIPTION (Adapted from the applicant's abstract and specific aims): The gas-exchange surface of the lung is continuously challenged by inhaled particulate antigens, however, the generation of a T-cell mediated immune response within the lung is uncommon. The development of a pulmonary immune response reflects the net effects of proinflammatory and suppressive activities by immune cells in the lung. In this regard, alveolar macrophages (AM) play a pivotal role in the response to particulates by ingesting and sequestering them away from immune cells in the lung interstitium. Activated AM also secrete factors that effectively suppress the activities of antigen presenting cells (APC) and the proliferation of T-cells. Dendritic cells (DC) distributed in the airway and pulmonary interstitium entrap inhaled soluble antigens and present them to T-cells in draining lymph nodes and lung. Although DC show limited phagocytosis, they can present particulate antigens to T-cells in vitro. The broad goal of this project is to understand how macrophages interact with DC and T-cells during a particulate antigen challenge to suppress the immune response in vivo. This project will address the following questions: Aim 1. How do soluble and particulate antigens differ in their abilities to promote NO production by AM? Aim 2. How does NO suppress the activities of lung DC and T-cells? Aim 3. How do phagocytosis and NO production by AM in vivo contribute to the development of immune "tolerance" to particulate antigens?