Effect of chemotherapy on suppressor T cells in BCG-infected mice

Specific pathogen-free B6D2 mice infected intravenously with 10(6) or 10(8) viable BCG Pasteur develop an anti-tuberculous immune response resulting in a progressive decline in viable BCG counts for the spleen and lung. Mice infected with 10(8) bacilli did not develop detectable levels of tuberculin hypersensitivity. Spleen cells harvested from both groups of mice at increasing time intervals after infection were T-cell enriched by nylon wool passage and tested for blast transformation following exposure to PHA or PPD. An early peak in tritiated thymidine uptake was observed following PPD exposure of cells from both the 10(6) and 10(8) groups. Cells from the latter group of animals developed a profound suppression to responsiveness to PPD throughout the remainder of the experiment. If the heavily infected mice were exposed to a regimen of 10 mg isoniazid plus 10 mg rifampin per 100 ml of drinking water for 30 days, the viable BCG population present within the lungs and spleen declined to near undetectable levels. This drop was associated with a decline in supressor T-cell activity demonstrated by appropriate cell-mixing experiments in vitro. The blastogenic responses to both PHA and PPD were substantially restored after 30 days of drug treatment. Treatment of the BCG infected mice within the first 7 days of infection prevented the development of the suppressor T-cell population.