REGULATION OF RAT PULMONARY DENDRITIC CELL IMMUNOSTIMULATORY ACTIVITYBY ALVEOLAR EPITHELIAL CELL-DERIVED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

The presentation and recognition of foreign antigen is the critical in itial event in the development of local immunity, In the lung, antigen -presenting cell activity is largely attributable to pulmonary dendrit ic cells (DC) that are distributed along the airways and throughout th e pulmonary interstitium in close proximity to overlying alveolar epit helial cells. To test the hypothesis that DC immunostimulatory activit y might be locally regulated by overlying alveolar epithelial cells, w e evaluated the ability of rat type II alveolar epithelial cells to in fluence the capacity of purified rat pulmonary DC to stimulate T-cell proliferation in an allogeneic, mixed leukocyte reaction. We found tha t alveolar epithelial cells greatly enhanced the ability of dendritic cells to induce T-cell proliferation. This effect on DC immunostimulat ory activity was mediated by a soluble factor preferentially secreted from the basolateral epithelial cell surface. Alveolar epithelial cult ures were found to express mRNA for granulocyte macrophage colony-stim ulating factor (GM-CSF), and blocking antibodies against GM-CSF partia lly neutralized the effect of epithelial cell-conditioned media on DC stimulatory activity, indicating that the effect was due at least in p art to alveolar epithelial cell-derived GM-CSF. Through the polar secr etion of GM-CSF, alveolar epithelial cells may play an important role in creating distinct immunologic environments within the lung.