Staphylococcal peptidoglycan suppresses production of interleukin-2 by T cells through a T cell-derived factor induced by direct contact between T cells and monocytes

During the last 2 decades, the incidence of sepsis due to gram-positive bacteria has increased dramatically. Nevertheless, effects of the cell-wall components that do not contain endotoxin, on immunity, are still largely unknown. Here, we demonstrate, for the first time, that the gram-positive bacterial cell-wall component peptidoglycan (PGN) severely inhibits the production of interleukin (IL)-2 by cultured human peripheral blood mononuclear cells stimulated with anti-CD3 and anti-CD28 antibodies. Furthermore, we provide evidence that the inhibitory effect is mediated predominantly by a soluble mediator produced by T cells and that the production of the inhibitory mediator is induced by direct cell-to-cell contact of T cells with PGN-stimulated monocytes. The T cell-derived inhibitory mediator is distinct from known immunosuppressive lymphokines, such as IL-10 and IL-4. In light of the key role of IL-2 in cell-mediated immunity, it can be suggested that PGN induces the dysfunction of cell-mediated immunity.