In vitro induction of nonspecific resistance in macrophages by specifically sensitized lymphocytes

Experiments were carried out to determine whether macrophages can be activated in vitro to resist challenge with heterologous microorganisms. Sensitized spleen cells from guinea pigs chronically infected with Toxoplasma gondii were cultured with normal guinea pig peritoneal macrophages in the presence and absence of Toxoplasma antigen. Macrophage monolayers incubated with sensitized spleen cells and antigen were markedly resistant to challenge from Listeria monocytogenes. Resistance was manifested by prolonged survival of the monolayers and rapid intracellular killing of the bacteria. Macrophages incubated with sensitized spleen cells but in the absence of antigen, as well as macrophages cultured with normal spleen cells, in the presence or absence of antigen, were rapidly destroyed. Sensitized spleen cells responded to the presence of Toxoplasma antigen by increased uptake of tritium-labeled thymidine. Supernatant fluid medium obtained from cultures of macrophages, sensitized spleen cells, and antigen contained a macrophage migration inhibitory factor(s). In addition, these supernatant fluids were capable of inducing increased resistance to Listeria in normal macrophages.