Quercetin inhibition of the induction and function of cytotoxic T lymphocytes

Quercetin is a naturally occurring flavonoid, chemically related to cromolyn. Quercetin has been shown to inhibit antigen- and mitogen-induced histamine release from rat mast cells and basophils of subjects with hay fever, to increase cyclic adenosine monophosphate (AMP) in Ehrlich ascites tumor cells and to inhibit phosphodiesterase and certain adenosine triphosphatase (ATPase) systems. We have studied the effect of quercetin on mouse T cell responses. When 5 x 10(-6) to 5 x 10(-5) M quercetin is present throughout either allogeneic mixed leukocyte culture (MLC) or cytotoxic T lymphocyte (CTL) assay culture, inhibition of in vitro CTL generation or effector function results, respectively (inhibition is 75-100% at 2 x 10(-5) M and 100% at 5 x 10(-5) M). Quercetin also inhibits concanavalin A-induced DNA synthesis. Addition of Cu2+ strongly blocks the effects of quercetin in all systems tested, in a concentration dependent fashion, while Mg2+ and Ca2+ have little or no effect and Mn2+ and Co2+ have a significant but slight blocking effect on quercetin-mediated inhibition of both CTL generation and function. In kinetic studies, evidence was obtained for the existence of a major quercetin-sensitive step in CTL induction, between 3 and 24 hr of the MLC.