Ganglioside control over IL-4 priming and cytokine production in activated T 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 IL-4 synthesis by naive CD4(+) T cells, Our present studies have characterized responsible sialoconjugate targets of Neu-1 and questioned possible biochemical mechanisms responsible for their regulatory influences on IL-4 gene expression, These studies determined that treatment of T cells with the naturally 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 restimulated 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 attenuated the level of calcium influx following CD3 epsilon crosslinking, and CD4(+) T cells from Neu-1-deficient B10.SM strain mice (neur-1(alpha) and IL-4-deficient) expressed reduced levels of intracellular calcium following activation, Our results indicate that activities by membrane gangliosides can influence the cytokine programs in CD4(+) T cells, possibly through the modulation of calcium responses induced by T cell activation. (C) 2000 Academic Press.