I. STUDIES ON THE MECHANISMS OF MACROPHAGE ACTIVATION Destruction of Intracellular Leishmania enriettii in Macrophages Activated by Cocultivation with Stimulated Lymphocytes* BY JACQUES MAUEL, YOLANDE BUCHMULLER, A~u~

When interacting with sensitized lymphocytes stimulated by antigen, macrophages undergo a number of metabolic and functional changes, generally referred to as "activation". I One distinct feature of activated macrophages is their enhanced capacity to restrict the growth of, or destroy ingested microorganisms (2, 3). In particular, it has recently been shown that under certain conditions, activated macrophages may display considerable cytotoxic activity in vitro towards certain protozoan parasites (4-7). Leishmania parasites are obligate intracellular protozoa which may infect various species of vertebrate hosts, and display a predilection for cells of the mononuclear phagocyte system (8). Preliminary experiments from this laboratory indicated that Leishmania enriettii, a parasite of the guinea pig, was readily endocytosed by mouse peritoneal macrophages in vitro, in which it would reside essentially unharmed unless an activating stimulus induced the cells to destroy the micro-organism (4, 9, 10). Killing of L. enriettii in mouse m_acrophages thus constitutes a convenient model system with which to study the mechanisms of activation. The present report describes the effect of cocultivation with lymphocytes stimulated by allogeneic cells, and by the T-cell mitogen concanavalin A (Con A), 2 on the capacity of mouse macrophages to destroy ingested L. enriettii. Results of studies on the effects of soluble factors released by such stimulated lymphocytes will be presented in separate articles.