BRAIN-DERIVED GANGLIOSIDES INDUCE CELL-CYCLE ARREST IN A MURINE T-CELL LINE

Gangliosides modulate various T cell effector functions through poorly defined mechanisms. To begin to understand one of their effects, the present study examined how normal brain-derived gangliosides suppress T cell proliferation using the murine T cell line, EL4, as a model. Ga ngliosides inhibited EL4 cell growth by causing progressive cell cycle arrest. Dephosphorylation of the retinoblastoma protein (pRB) appeare d to be the principal mechanism through which this effect was produced . Since okadaic acid could reverse both the growth arrest and pRB deph osphorylation, gangliosides may activate a phosphatase to mediate thes e events. Taken together, these data have implications for understandi ng how the local proliferation of T cells exposed to endogenous gangli osides within the brain may be regulated. (C) 1998 Elsevier Science B. V. All rights reserved.