Response of congenitally athymic (nude) mice to infection with Mycobacterium bovis (strain BCG).

Mice homozygous for the mutation "nude" (nu/nu) are athymic and lack thymus-dependent lymphocytes. Heterozygote (nu/+) controls, which are phenotypically and immunologically normal, and (nu/nu) mice were infected with 1.0 times 10-6 colony-forming units of Phipps strain BCG. In the spleens of nu/+ mice, there was a progressive increase in number of BCG up to the second week, followed by a gradual decline. However, in the nu/nu mice, BCG growth was gradual and continuous until termination of the experiment at 5 weeks. In the lung, significant differences were not noted until after the second week, at which time the nude mice showed a rapid increase (of more than 2 log10) in the number of BCG. However, the number of BCG was not significantly greater in the livers of either group. Changes in the normal histology of the lung included a massive influx of monocytes during the first 2 weeks which peaked at day 21. In the lungs of the nu/+ mice by day 28, there was considerable granuloma formation consisting of monocytes and small lymphocytes. However, in the lungs of nu/nu animals, the granulomas were made up primarily of monocytes with a lack of small lymphocytes. Acid-fast stains confirmed the presence of large numbers of organisms in the macrophages of nu/nu mice, with gradual destruction of these phagocytic cells.