Development of suppressor T cells in mice heavily infected with mycobacteria.

Specific pathogen-free B6D2 mice were infected intravenously with 10(8) viable BCG, M. habana or M. simiae and the level of tuberculin hypersensitivity to 2.5 micrograms PPD or cytoplasmic protein antigens (CPA) prepared from the other organisms was determined using the footpad swelling test with increasing time after infection. This was correlated with the growth or persistence of mycobacterial populations within the liver. Spleen cells were removed from these infected mice and the level of blast transformation following exposure to PHA, PPD or M. habana or M. simiae CPA was measured in vitro. Early in the mycobacterial infections (day 14) thymidine incorporation by the spleen cells was significantly enchanced followed by a profound depression in incorporation rates as the infection progressed. The mechanism of this depressed response involved the production of suppressor T cells in the spleen. In the case of the M. simiae or M. habana infection, cells capable of mediating suppression were still present even after 12 months of infection. In the BCG infection, suppressor T cells declined with time so that by 4 months incorporation rates were back to normal and suppressor cells were no longer detectable in the spleens of the infected animals.