IL-2 and IL-15 Exhibit Opposing Effects on Fas Mediated Apoptosis

(整期优先)网络出版时间:2004-02-12
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IthasbeenshownthatIL-2andIL-15canhaveopposingeffectsonlifeanddeathofTcells.However,theroleofIL-2andIL-15inregulatingthefateofothercelltypesislessclear.Inthepresentstudy,weexaminedtheimpactofIL-2andIL-15onlifeanddeathofpre-BcellsusingtheBAF-B03line.WeshowedthatBAF-B03cellsconstitutivelyexpressedtheprivateIL-2RαchainandIL-15Rαchain,andthesharedIL-2Rβchainandγcchain.StimulationofBAF-B03cellsinvitrowithIL-2andIL-15inducedvigorouscellproliferationinadose-dependentfashion.TitrationofIL-2andIL-15intheassayshowedthatthemitoticeffectsofIL-2andIL-15wereremarkablysimilar,Howerer,thesensitivitiesofBAF-B03cellstoFasmediatedapoptosisafterIL-2andIL-15stimulationwerestrikinglydifferent.CellsculturedinIL-2readilyunderwentapoptoticcelldeathuponcross-linkingoftheFasreceptorwhereascellsculturedinIL-15wereextremelyresistanttoFastriggeredcelldeath.Theanti-apoptoticeffectofIL-15inthismodelwasassociatedwithincreasedexpressionofBcl-xL.FLIPexpression,however,wascomparablebetweenIL-2andIL-15stimulatedcells.WeconcludethatIL-2andIL-15havediametricallyoppositeeffectonthefateofBAF-B03cells,althoughbothcytokinessharesimilarreceptorstructureandexhibitsimilarmitoticactivities.