Characterization of dendritic cell populations in the respiratory tract.

Research in a variety of experimental animal species and in humans has identified dendritic cells (DCs) as the principal resident antigen presenting cells in respiratory tract tissues. The two major populations of respiratory tract DC (RTDC) comprise those found in the parenchymal tissues of the peripheral lung and in the epithelium of the conducting airways, in which they are distributed as a contiguous network comparable to the langerhans cells (LC) of the epidermis. Under steady state conditions, the airway DC population turns over every 36-48 h, whereas those in the lung parenchyma display a half-life of approximately 7 days. However, under conditions of local stress (e.g., inflammatory challenge), the turnover of these RTDC populations further accelerates, reflecting their important role in local antigen surveillance. In the resting state, they are specialized for the efficient endocytosis and processing of internalized antigens, but lack the capacity to efficiently present antigen to T-cells until they receive appropriate cytokine signals (especially GM-CSF); responsiveness to the latter is inhibited by nitric oxide, in particular from adjacent lung tissue macrophages. Our most recent findings indicate that the "default" function of resting RTDC involves selective priming for Th2 responses, and induction of optimal Th1 responses requires exposure to GM-CSF together with TNFalpha or CD40L.