The potentiating, mitogenic and inhibitory effects on lymphocytes in vitro, of macrophages in the lymph nodes of mice 'overloaded' with mycobacterial products.

The lymph nodes of mice overloaded with mycobacterial products, either by the injection of whole or ultrasonicated organisms, or as a consequence of severe infection with Mycobacterium ulcerans, contain phagocytic cells which cause spontaneous transformation of the lymph node cells in a low volume, high cell density culture system. This spontaneous mitosis is unaffected by trypsinization but is inhibited by specific antigen and by PHA, and eliminated by treatment with carbonyl iron. Replacement of the macrophages removed with carbonyl iron by a critical number of peritoneal cells, restores the spontaneous transformation. Normal lymph node, thymus or peritoneal lymphocytes will also undergo mitosis if small numbers of peritoneal cells are added to them. This phenomenon therefore appears not to be antigen-dependent, but is probably due to a mediator released from macrophages. The possible role of this phenomenon in the pathogenesis of mycobacterial disease and the 'overloading' of T lymphocytes in vivo is discussed, with reference to similar macrophage-dependent mechanisms reported in other systems.