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

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 GM2 was most inhibitory (I50 = 15 microM). GD1a and GT1b were somewhat less potent, whereas GM1 and GM3 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.