Abstract:
<p>Due to its nature and function, the lungs are confronted with the unique challenge of rapidly eliminating inhaled pathogens and particulates while limiting inflammatory responses. A disruption in this immune homeostasis may result in respiratory inflammatory diseases, such as allergies or asthma. The alveolar epithelial type II cell and its secretory product, surfactant protein A (SP-A), have been linked to roles in adaptive immunity in the lung. The discovery that type II cells constitutively express major histocompatibility complex class II (MHC II) suggested that type II cells may function to present antigen to T cells. Studies in vitro demonstrated that SP-A inhibits the maturation of bone marrow-derived dendritic cells. The goal of this work was to determine how type II cells and SP-A may be functioning to regulate adaptive immunity in the lungs. The hypothesis tested is that type II cells and SP-A suppress the activity of T cells and dendritic cells in the lungs. As T cells and dendritic cells are critical for the initiation and function of the adaptive immune response, the inhibition of T cell and dendritic cell activity would limit inflammation in the lungs. Although isolated murine type II cells expressed MHC II, they did not express detectable levels of the costimulatory molecules CD80 and CD86 and were poor activators of T cells. Upregulation of MHC II on type II cells by interferon-gamma stimulation did not enhance the ability of type II cells to activate T cells. Instead, the type II cells suppressed T cells from subsequent activation to antigen in an antigen-dependent manner, indicative of tolerance. T cells pre-incubated with type II cells and antigen were suppressed from further activation, even after removal of the type II cells. Using a model of pulmonary infection with Mycoplasma pneumoniae, wildtype mice were found to have fewer mature dendritic cells in the mediastinal lymph nodes than SP-A null mice. The presence of SP-A in the wild-type mice had a suppressive effect on the M. pneumoniae-induced maturation of dendritic cells in the lungs. Together, the data demonstrate that type II cells and SP-A participate in the adaptive immune response by suppressing the activity of T cells and dendritic cells in the lungs.</p>
