Development of immunity to tuberculosis in adult mice injected with tubercle bacilli during foetal life

Abstract

The methods successfully used to induce immunological tolerance in mice to a variety of antigens were applied to studies on mycobacterial antigens (whole tubercle bacilli). Mice were injected with approximately 5×10⁵ living attenuated (BCG) or heat-killed virulent (H₃₇Rv) tubercle bacilli on the 15th, 16th or 17th day of foetal life. Acid-fast bacilli were found in the lungs, spleens and livers of these mice after birth. Such mice subsequently developed normally and were not more susceptible to BCG than mice primarily infected in adult life.

The immunological state of the mice exposed to mycobacteria in utero was determined by challenging 5 to 6 weeks after birth with either virulent or attenuated tubercle bacilli. These tests showed that an intra-embryonic injection of mycobacteria resulted in protective immunity and not tolerance. Furthermore, the mice also showed delayed-type hypersensitivity to mycobacteria.

These results are discussed in relation to the ability of other antigens to induce immunological tolerance in mice and to the response of other animal species to mycobacteria.