Effect of Bacillus Calmette-Guérin on the in vitro generation of cytotoxic T lymphocytes. II. Role of interleukin-1-like factors and of soluble suppressor factors.

The injection of BCG vaccine in C57BL/6J mice results in the suppression of the generation of cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC) and of mitogenic reactions to concanavalin A (Con A). Suppression is mediated by macrophage-like suppressor cells. Since previous work had indicated that suppression involved the inhibition of the production of interleukin-2 (IL-2), the effects of BCG on interleukin-1 (IL-1), a monokine required for IL-2 production, were investigated. It was found that the release of IL-1-like activity in spleen cell cultures stimulated with LPS or Con A was increased by previous BCG treatment of the cell donors. In MLC, the release of IL-1-like activity was also increased by BCG. However, the detection of IL-1-like activity in MLC supernatants was prevented by the presence of a suppressor factor. In this case, the IL-1-like activity could be separated with gel filtration from the suppressor factor which had higher molecular weight. The production of IL-1-like activity by CBA/J spleen cells, which are not suppressed by BCG, was not significantly different from that of C57BL/6J cells, which are markedly suppressed. Moreover, the addition of IL-1 to the BCG-suppressed cultures not only did not restore normal reactivity, but actually further suppressed CTL formation. It was concluded that BCG-induced suppression cannot be attributed to decreased IL-1 activity. The suppressor factor discovered during these investigations may have a role in this type of suppression.