Ganglioside control over IL-4 priming and cytokine production in activatedT cells

Our previous studies have shown that the enzymatic activities of Neu-1, an endogenous sialidase encoded in the murine MHC, are involved in promoting I L-4 synthesis by naive CD4(+) T cells, Our present studies have characteriz ed responsible sialoconjugate targets of Neu-1 and questioned possible bioc hemical mechanisms responsible for their regulatory influences on IL-4 gene expression, These studies determined that treatment of T cells with the na turally occurring ganglioside GM3 inhibited the production of IL-4 without affecting the production of IL-2, An analysis of IL-4-primed CD4(+) T cells further demonstrated that GM3 treatment specifically inhibited the restimu lated production of IL-4, IL-5 and IL-13, without inhibiting the production of IL-2 and IFN-gamma. The inhibitory effects of GM3 could be overcome by treatment with thapsigargin or ionomycin, suggesting ganglioside regulation occurs upstream of activation-induced calcium mobilization GM3 treatment a ttenuated the level of calcium influx following CD3 epsilon crosslinking, a nd CD4(+) T cells from Neu-1-deficient B10.SM strain mice (neur-1(alpha) an d IL-4-deficient) expressed reduced levels of intracellular calcium followi ng activation, Our results indicate that activities by membrane ganglioside s can influence the cytokine programs in CD4(+) T cells, possibly through t he modulation of calcium responses induced by T cell activation. (C) 2000 A cademic Press.