INHIBITION OF HUMAN PERIPHERAL-BLOOD MONONUCLEAR CELL PROLIFERATIVE RESPONSE BY GLYCOSPHINGOLIPIDS FROM METACESTODES OF ECHINOCOCCUS-MULTILOCULARIS

The effect on human peripheral blood mononuclear cells (PBMCs) of neut ral glycosphingolipids extracted from metacestodes of the parasite Ech inococcus multilocularis was investigated. Neutral glycosphingolipids inhibited [H-3]thymidine uptake by human PBMCs upon stimulation by mit ogens such as phytohemagglutinin A and pokeweed mitogen or by allogene ic Burkitt B cells. This effect,vas dose dependent and was related to a decrease in interleukin 2 (IL-2) synthesis, the expression of IL-2 r eceptors (CD25) being unmodified, Addition of exogenous recombinant IL -2 restored the cell proliferation. Partial inhibition of immunoglobul in G (IgG), IgA, and IgM synthesis was observed in the supernatant of cell culture in association with the inhibitory effect. Identification of active subfractions contained in the neutral glycosphingolipid fra ction was also studied in relation to cell viability. The free ceramid e fraction had an inhibitory effect, in part related to cell lysis, pa rticularly at high concentration, while the monogalactosylceramides ha d a paradoxical effect: as an activator at low concentrations and as a n inhibitor at high concentrations, with limited cell survival. The im munogenic neutral glycosphingolipids containing at least two carbohydr ate residues, all having a structure based on Gal beta 1-->6Gal, were inhibitors of PBMC proliferation and showed good cell survival. These results suggest that parasite neutral glycosphingolipids mag play an i mmunologically relevant role in alveolar hydatid disease.