Mechanisms of action of Mycobacterium bovis BCG-induced suppressor cells in mitogen-induced blastogenesis.

Spleen cells from Mycobacterium bovis BCG-infected C57B1/6 mice when cultured in vitro for 72 h elicited soluble suppressor mediators capable of nonspecifically suppressing the mitogen-induced blastogenesis of normal splenocytes. Maximal production of suppressor mediators occurred during the first 24 h in culture, and their production ceased after 72 h. Attempts to isolate the mediators from fresh nonincubated splenocytes failed. After incubation, a strong residual suppressive activity was constantly detected in cell preparations used for production of suppressor factors. Supernatants prepared from cultures of spleen cells of mice infected 14 days earlier possessed higher suppressive activity than did those obtained 28 days after infection. In contrast, the residual cellular suppressive activity increased during the course of the infection. Although the activity of soluble factors was not inhibited, the residual activity of incubated cells was highly depressed by the presence of mouse erythrocytes in the cultures. Thus, the incubated cells appear to act through a direct cell-to-cell contact with the mitogen-responding cells. Finally, the results of depletion experiments suggest that the two populations of BCG-induced suppressor cells, namely, T lymphocytes and macrophage-like cells, are able to elicit suppressor mediators and to retain thereafter suppressive activity.