The immunoregulatory effects of gangliosides involve immune deviation favoring type-2 T cell responses

Abstract

Gangliosides, sialic acid-containing glycosphingolipids present in most cell membranes, are thought to participate in the maintenance of immune privilege and tumor-induced immunosuppression. However, the mechanisms responsible for their immunomodulatory activity remain poorly understood. The purpose of this study was to investigate whether gangliosides are able to modulate the balance of type-1/type-2 T cell responses and to characterize the cellular mechanisms involved. The effects of different gangliosides on anti-CD3-stimulated murine splenocytes and purified T cells were studied. The presence of gangliosides during T cell activation reduced the expression of interferon-gamma (IFN-gamma) and enhanced that of interleukin (IL)-4, suggesting a shift toward a type-2 response. Intracellular cytokine staining demonstrated that gangliosides inhibited IFN-gamma production in CD4+, CD8+, and natural killer (NK)1.1+ cell populations and enhanced IL-4 in CD4+ T cells. The ganglioside-mediated enhancement in IL-4 production was independent of changes in endogenous IFN-gamma, did not occur with cells from CD1d-deficient mice, and was partially inhibited by anti-CD1d antibodies. The inhibitory effects on IFN-gamma were independent of endogenous IL-4 or the presence of NKT cells and were unaffected by anti-CD1d antibodies. These results suggest that gangliosides may modify the immunological environment by promoting immune deviation in favor of type-2 T cell responses.