Ling Zhi-8: a novel T cell mitogen induces cytokine production and upregulation of ICAM-1 expression.

Ling Zhi-8 (LZ-8) is a protein purified from Ganoderma lucidium, a Chinese medicinal fungus thought to possess potent effects on the immune system. When examined for its effects on lymphocytes, LZ-8 exhibited potent mitogenic effects on human peripheral blood lymphocytes (PBL), inducing a bell-shaped dose-response curve similar to that caused by PHA and other lectin mitogens. Fractionation experiments indicated that the proliferative response in the PBL cultures was primarily due to T cells, but was monocyte dependent. Stimulation of PBL with LZ-8 resulted in the production of IL-2 and a corresponding upregulation of IL-2 receptor expression. In addition to T cell proliferation, microscopic examination of LZ-8-stimulated PBL revealed that LZ-8 induced cellular aggregate formation. The aggregate formation correlated with a dramatic rise in ICAM-1 expression and an increased production of IFN-gamma, TNF alpha, and IL-1 beta, molecules associated with regulation of ICAM-1 expression. Both the aggregate formation and the proliferative effects of LZ-8 were blocked by addition of monoclonal antibody to either CD18 or CD11a, the counterreceptor complex components for ICAM-1. Furthermore, addition of neutralizing antibodies to both IL-2 receptor and TNF alpha blocked aggregate formation, cellular proliferation, and ICAM-1 expression. These findings demonstrate that LZ-8 is a potent T cell activator, mediating its effects via cytokine regulation of integrin expression.