Immunogenicity of an aerogenic BCG vaccine in T-cell-depleted and normal mice

Abstract

Aerogenic infection of adult thymectomized, lethally irradiated, bone marrow-reconstituted (THXB) C57B1 times C3H F1 hybrid mice with 1 to 3,000 viable BCG Montreal was followed by an extended period of logarithmic growth to a maximum population of 5 times 10-6 bacilli by day 35. The infection spread to the liver, spleen, and bone marrow with extensive multiplication in all test organs before the growth curves abruptly entered a stationary phase. Up to 30% of the THXB mice eventually died as a result of the ongoing BCG infection. There was no sign of an antimicrobial immune response in the THXB mice analogous to that seen in the control animals beginning about day 30. The THXB mice developed considerable immediate but no delayed hypersensitivity to PPD. Intravenous challenge of the BCG-vaccinated THXB mice with 105 virulent Mycobacterium tuberculosis Erdman indicated that they were as susceptible to the tuberculous challenge as a group of unvaccinated controls. Visible surface lesions developed on the lung 90 days postinfection in the T-cell-depleted host with a sharp rise in counts to 175 per lobe on day 120 followed by a plateau for the remainder of the study. Control mice developed visible lesions about day 50, with 225 lesions per lobe by day 70 and a sharp decline to undetectable levels by day 90. The histopathology of these changes was examined carefully, together with the rate of cellular proliferation (tritiated thymidine uptake) by lung and spleen cells as the BCG infection progressed in the THXB mice. Peak uptake by both organs was depressed during the early stages of the BCG infection in the T-cell-depleted mice, but later the incorporation rates were significantly elevated above control values as the infection progressed.