Accessory cells of the lung. I. Interferon-gamma increases Ia+ dendritic cells in the lung without augmenting their accessory activities

Abstract

Dendritic cells are specifically adapted to provide accessory signals for the growth of T lymphocytes. Ia+ dendritic cells are present within the normal lung; however, little is known concerning their regulation in vivo. Interferon-gamma (IFN-gamma) is a proinflammatory lymphokine that augments the expression of Ia antigens and promotes the accessory activities of a variety of cells. In order to determine whether IFN-gamma regulates pulmonary dendritic cells in vivo, Lewis rats were injected intraperitoneally with recombinant murine IFN-gamma (2 x 10(5) U/rat/day) or with buffered saline for 5 consecutive days. Following sacrifice, the lungs were excised, and the distribution and number of Ia (OX-6)+ cells was determined in situ. Dendritic cells were localized in the mucosal lining of the tracheobronchial tree, in pulmonary capillaries, as well as in the alveolar septal interstitium and subjacent to the pleural surfaces. IFN-gamma yielded a specific increase in Ia+ dendritic cells in alveolar septa and in pulmonary airways. Purified Ia+ dendritic cells from enzymatic digests of lung were excellent accessory cells for the proliferative responses of both antigen-primed and naive T lymphocytes. IFN-gamma did not, however, further augment the expression of Ia antigens or the accessory activities of pulmonary dendritic cells. These results suggest that IFN-gamma may promote pulmonary T cell-mediated inflammatory responses in vivo by increasing the number of Ia+ dendritic accessory cells in the lung.