Collagenase digestion of tissue slices from perfused, lavaged SPF rat lung released approximately 10(8) viable mononuclear cells per gram tissue, which comprised 35% T lymphocytes and up to 26% macrophages. A subset of these cells that were Ia+, surface Ig-, nonadherent, FcR- and of ultra low density (putative dendritic cells [DC]), presented protein antigen to immune T cells in vitro, and this function was inhibited by the presence of low numbers of endogenous adherent, FcR+ cells (putative macrophages). APCs were also identified in digests from tracheal epithelium, and were shown to bind antigen in immunogenic form as a result of natural (inhalation) exposure in vivo. Immunoperoxidase staining of frozen sections revealed populations of strongly Ia+ cells with prominent DC-like morphology within the alveolar septal walls and the tracheal epithelium; in both areas, they were closely associated with pleiomorphic cells that expressed macrophage surface markers. We accordingly postulate that interactions between Ia+ antigen-presenting DCs and endogenous tissue macrophages play an important role in regulating T cell activity in the respiratory tract.

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