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.
Nakagawa
Yukari
Y
Society of Japanese Pharmacopoeia, Osaka Branch, Osaka, Japan.
Murai
Toshimi
T
D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002452:Cell Count; D017077:Culture Media, Conditioned; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology
D018106:CD28 Antigens; D017252:CD3 Complex; D017077:Culture Media, Conditioned; D007376:Interleukin-2; D010457:Peptidoglycan; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma