What T Cells Tell Macrophages to do during Resistance to Listeriosis

Abstract

Current understanding of cell-mediated immunity originated with the elegant experiments of Mackaness and colleagues (1,2). These investigators recognized that antigen-specific thymus-derived lymphocytes, T cells, stimulated non-specific macrophages to express high levels of anti-microbial activity. These experiments, completed in the 1960’s, laid the foundations for a model still widely accepted today. However, as with most biologic processes, we have come to understand that events are more complicated than they originally seemed. Recent evidence suggests that while this model may describe T cell-mediated activation of macrophages to kill tumor cells and obligate intracellular microbes, it may not describe the events which occur during induction of resistance to infection by facultative intracellular organisms, particularly facultative intracellular bacteria. The discussion below describes experiments conducted by us and by others which suggest that the primary role of T cells in resistance to infection by Listeria monocytogenes, a facultative intracellular bacterium, is not to activate the macrophage. Rather, the major role of the T cell seems to be to cause recruitment of inflammatory cells, both macrophages and neutrophils, which express high levels of bactericidal activity. Many of these ideas have been expressed in a recent article (3).