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. Gangliosides inhibited EL4 cell growth by causing progressive cell cycle arrest. Dephosphorylation of the retinoblastoma protein (pRB) appeared to be the principal mechanism through which this effect was produced. Since okadaic acid could reverse both the growth arrest and pRB dephosphorylation, gangliosides may activate a phosphatase to mediate these events. Taken together, these data have implications for understanding how the local proliferation of T cells exposed to endogenous gangliosides within the brain may be regulated.
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dirani@welchlink.welch.jhu.edu
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D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005732:Gangliosides / Q000378:metabolism / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000201:enzymology; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*
D005732:Gangliosides; D016160:Retinoblastoma Protein; D010744:Phosphoric Monoester Hydrolases