Lymphocyte-Macrophage Interactions in BCG-Treated Mice

Abstract

A previous study to investigate the mode of action of BCG showed that in mice, adjuvant modulated some immune responses via an action on macrophages (4). Indeed, splenic macrophages were responsible for the unresponsiveness of the T-lymphocytes to mitogens in vitro observed after BCG injection, whereas such a response was unaffected in B-lymphocytes. In addition, peritoneal macrophages were activated as shown by their capacity to kill non-specifically tumor cells in vitro. These findings showed that BCG could simultaneously exert stimulating and inhibitory effects through macrophage and lymphocyte interactions. These results were observed after injection of 1 mg of BCG. The question arises whether increasing doses of adjuvant could modify the level of macrophage activation, the production of inhibitory macrophages, and perhaps extend their suppressive activity to both T- and B-lymphocytes. Indeed, injection of high doses of BCG were shown to depress the antibody response to sheep red blood cells (6) and to inhibit the capacity of T-lymphocytes to elicit a graft-versus-host reaction (5). Perhaps all schedules that induce immune stimulation by BCG may have the adverse side effect of inhibiting lymphocyte functions.