T-cell-mediated immunity in persistent Mycobacterium intracellulare infections in mice

Abstract

Growth of mouse-virulent Mycobacterium intracellulare D673 and TMC 1405 in the lung was affected by T-cell depletion in susceptible C57BL/6 mice. Significant differences also occurred between the growth patterns seen in congenitally athymic (nu/nu) mice and their nu/+ littermates. Treatment of the mice with an immunosuppressive regimen of cyclosporin A (75 mg/kg of body weight per day subcutaneously) provided further evidence of the importance of T cells in controlling growth of M. intracellulare in the normal host. Adoptive transfer experiments indicated the presence of a T-cell-mediated specific protective immunity against a subsequent M. intracellulare challenge when transfer was carried out 3 weeks after immunization of the donor host. At this time, cross-protective immunity was also observed against a virulent M. tuberculosis challenge. There was no difference in the rate of growth by M. intracellulare as challenge in Mycobacterium bovis BCG-activated or normal peritoneal macrophages from C57BL/6 mice tested in vitro during a 7-day period. However, M. tuberculosis growth rates were decreased substantially in the BCG-activated macrophages. These studies suggest that mice infected with M. intracellulare do not eliminate the infection, because this organism can resist the bactericidal activity of the T-cell-activated macrophage better than M. tuberculosis can.