Lymphocyte-mediated modification of blood-derived macrophage function in vitro; inhibition of growth of intra-cellular mycobacteria with lymphokines.

Evidence is presented, based on in vitro model-systems, that lymphokine-like agents and lymphocytes can elicit in vitro changes in macrophages which replicate those observed in vivo associated with cell-mediated immunity. (1) Supernatants (containing lymphokines; filtered or unfiltered) from mixed leucocyte cultures (MLC) from two genetically different rabbits activated rabbit blood-derived macrophages cultured in vitro. Activation comprised proliferation, presence of intracellular phase-lucent vacuoles, elongation and formation of intercellular cytoplasmic bridges and giant cells. No such activation was obtained with supernatants from unmixed leucocyte cultures. (2) Macrophages cultivated in MLC supernatants, but not unmixed leucocyte supernatants, inhibited the intracellular multiplication of mycobacteria, including the vole bacillus and Mycobacterium lepraemurium. (3) Similar macrophage activation was obtained in cultures of blood-derived macrophages exposed to M. leprae in vitro from patients with tuberculoid leprosy (high resistant form) in the presence of lymphocytes. No such activation was obtained in absence of lymphocytes. Under similar conditions no activation was observed in cultures of macrophages from patients with lepromatous leprosy (low resistant form of the disease).