Research in a variety of experimental animal species and in humans has iden
tified dendritic cells (DCs) as the principal resident antigen presenting c
ells in respiratory tract tissues. The two major populations of respiratory
tract DC (RTDC) comprise those found in the parenchymal tissues of the per
ipheral 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 popula
tion 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 str
ess (e.g., inflammatory challenge), the turnover of these RTDC populations
further accelerates, reflecting their important role in local antigen surve
illance. In the resting state, they are specialized for the efficient endoc
ytosis and processing of internalized antigens, but lack the capacity to ef
ficiently present antigen to T-cells until they receive appropriate cytokin
e signals (especially GM-CSF); responsiveness to the latter is inhibited by
nitric oxide, in particular from adjacent lung tissue macrophages. Our mos
t recent findings indicate that the "default" function of resting: RTDC inv
olves selective priming for Th2 responses, and induction of optimal Th1 res
ponses requires exposure to GM-CSF together with TNF alpha or CD40L.