Anthony Schwartz

Histamine inhibition of the in vitro induction of cytotoxic T-cell responses☆

Addition of 10-3 to 10-6 M histamine (H)3 to mixed leukocyte cultures (MLCs) inhibited primary in vitro induction of cytotoxic T lymphocytes (CTLs) specific for either allogeneic or trinitrophenol-modified syngeneic target cells. The use of specific H agonists implicated H2 but not H1 receptor triggering in the mediation of these effects. Unlike in vivo-induced allogenic CTLs, the addition of H to assay culture failed to influence the effector function of in vitro-induced CTLs of either specificity. Kinetic studies showed that this difference might be due to loss of functional H receptors after the initiation of the in vitro MCL, and demonstrated that H interferes with an early event in the generation of CTLs. These data indicate that H receptors are not merely markers for CTL precursors, but that they are functional receptors, and suggest that H may play an important role in regulating both the generation and effector function of CTLs in vivo.

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.

Histamine inhibition of concanavalin A-induced suppressor T-cell activation

Abstract In vitro exposure to concanavalin A (Con A) results in the induction of T cells which suppress the in vitro generation of trinitrophenol (TNP)-modified self-specific cytotoxic T lymphocytes (CTLs). Such suppressor populations do not contain detectable CTLs or CTL precursors specific for TNP-modified syngeneic target cells. Histamine (10 −3 M ) inhibits both the DNA synthetic response and the generation of suppressor T lymphocytes induced by Con A.