The relationship of delayed hypersensitivity to acquired antituberculous immunity: I. Tuberculin sensitivity and resistance to reinfection in BCG-vaccinated mice

Abstract

Specific pathogen-free mice were infected intravenously with different strains of BCG or with M. tuberculosis H 37R v. Despite marked differences in the resulting levels of tuberculin sensitivity, mice of all groups were comparable in their resistance to challenge with an isoniazid-resistant strain of BCG. A highly virulent strain of M. tuberculosis (Erdman) was no more resistant to inactivation in the tissues of immunized mice than was the drug-resistant strain of BCG. Mice which had been infected with 10 5 M. tuberculosis (Erdman) showed extensive growth of the organism in lung, liver, and spleen; tuberculin sensitivity appeared early, increased rapidly, and then declined. This phenomenon of desensitization was not observed in animals infected with comparable numbers of BCG, but did occur with larger doses of BCG (10 8). Spleen cells from these animals were as capable of conferring tuberculin sensitivity upon normal recipients as were cells from tuberculin-sensitive donors. Thus, an absence of peripheral sensitivity does not imply that immunologically committed cells are lacking from the tissues. When animals were challenged with virulent tubercle bacilli 3, 12, and 28 weeks after vaccination, they responded promptly with a major rise in tuberculin sensitivity, thereby demonstrating a persisting memory for mycobacterial antigens. This would explain why specific resistance showed little tendency to wane despite loss of tuberculin sensitivity.