The young of many species lack full immunocompetence at birth which may be due to a functional immaturity of the cells involved, or the presence of certain suppressor mechanisms. We examine the maturation of certain attributes of lung macrophages in the first three weeks of life of Lewis rats. These include: 1. Phagocytosis, 2. Fc receptor function, 3. C3 receptor function, 4. expression of I region associated (Ia) antigens, 5. interleukin I production, 6. fibronectin synthesis. Based on recent observations obtained from neonatal peritoneal macrophages, we postulate that prostaglandins, produced by macrophages within the lung, are one of the important factors mediating local suppression. This suppression is first examined in vitro in the context of antigen presentation in a genetically restricted manner using Listeria monocytogenes, an intracellular faculative bacterium which triggers a strong, virtually exclusive cell mediated immunity. Experiments are planned in which indomethacin is used to abrogate the suppressive effects of PGE2, and an in vitro generated lymphokine, with presumed gamma interferon activity, is used to stimulate neonatal alveolar macrophages to express surface Ia. Based on results obtained from in vitro experiments, studies are then carried out in neonatal rats, infected intratracheally with Listeria monocytogenes, to determine whether the administration of indomethacin and/or lymphokine ameliorate the severity of this pulmonary infection. Finally, experiments are devised to establish the distribution of alpha feto-protein within the lung and to determin wheter alpha fetoprotein plays a role in suppressing the immune function of alveolar macrophages in the neonatal period.
