Inhibition of interleukin-2-dependent cytotoxic T-lymphocyte growth by gangliosides

Abstract

Previous work has shown that exogenous gangliosides suppress lectin-induced T-lymphocyte mitogenesis in mixed populations of immune cells. As one potential cellular site of this inhibition, the influence of gangliosides on interleukin-2-dependent T-cell proliferation was tested, using cultures of cytotoxic T cells (strain CT-6). Incubation of CT-6 cells with mixed bovine brain gangliosides resulted in a dose-dependent inhibition of cell proliferation. Cell viability was unaffected by gangliosides, and the inhibition was totally reversed when the gangliosides were removed. Individual purified gangliosides were tested and GM 2 was most inhibitory (I 50 = 15 μM). GD, 1a and GT 1b were somewhat less potent, whereas GM 1 and GM 3 were only weakly inhibitory. Various nonpolar lipids, sulfatides, and sialic acid did not inhibit CT-6 cell growth. The results suggest that a primary mechanism whereby gangliosides inhibit lectin-induced lymphocyte mitogenesis is by inhibition of the interleukin-2-stimulated proliferation of T cells in these cultures.