The Immunopathogenesis And Synergy Of IL-12 And IL-18 In Adoptive Experimental Autoimmune Neuritis (AT-EAN)

Guillain一Barre syndrome(GBS)15 an acute infla"unatoryautoilnrnune disease affeoting myelin and axons ofthe PeriPheral nervoussystem(PNS).GBS has features of segmental demyelination with the;nfiitrationt of mox飞omielot一e)沈es The!,:一thol(,gy eha,:ges inelt:de earlylyxnphocytie infiltrates in sPinal ruots and Periplieral nerves,and5 tzbsequent maeroPhage一mediated,egmenLal,triPPing of myel一n.FxPerimentol出,toinlroune neuritis(EAN),a Paralytie illness in rodeniss]:,wsv七ry striking elinieal,neuroPhysi)logieal即d histological51而larities to GBS.Therefore,EAN serves as an useful model forexPloring theP川五ogenesis andir田刀unotheraPy of GBS.八dOPtiveeXPerimental aut oimmunene耐tis(户n飞EAN)can be adoPtively仃ansferred of Po or PZ一speeifie en4+T eells from别'mal with EAN. There 15 an evidence that abnormai oenular inunune reactions maybe involved in the Pa1Lhogenesis of EAN and Al'- EAN .RelatedPro垃nfiarnmatory cytokines,which secreted from Thl--t yPe cells,contribute to the tissued别叭age in EAN by changing the baiance be七刀eenthe eells of Thl and ThZ PhenotyPes in favor of Thl.ManyPro一idanl」11atory cytoklnes act as triggering events that are believedtoiultiate nerve damage.IL一12 and IL一18 both are the imPort呱pro一infl侧比unato万cytokines from Which eD4+Thz cells release.Theyhave syne堪etic effeet in enhancing the transeriPtion of IFN令.In thisstudy,we emPloyed a Passive EAN system to eval切ate the roles of吉林人学博十学位论文英文摘要IL一12 and IIJ一18 in the immunoPathogenesis of Al'- EAN and thesynergetie effect of tl,ese two eytokine,.Afte全suecessfully indueingEAN with pox:0.199 PePtides in lewis rats,we eultured lymPh node eell,and sPleen eells with PO一50一199,Promoting these T eells to Proliferate anddifferentiate.The eultured T cells have the ability in diserinlinating,memorizing and activating in inunune resPonse to the sPeeifie antigens ofPO一50一99.Then we eoeulture the aetivated PO一50一99 sPecifie T eells in thePresence of IL一1 2 and/or IL一1 8 before the transferation to the normalLewis rat.T eells stimulated飞vith anti一CD3 and anti一CD28 in the Presenceof IL一12 or IL一1 8 alone transferred mild exPerimental autoilnLmllnene一:riti,又EAN),vith ea:·lier。,nset,higher incidenee,later recovery,biggerarea 0.'demyelination and mofe lymPhoeytie infiltrates.These resultsindieate that 11,一12川飞d 11)一18 alonet欣ez〕art in the immunopathogene,15ofz\T- EAN.Ilowover, T cells coeultured with both eytokilles transferredmore severe elinical and histological EAN 51娜ficantly.w匕aiso detectIFN一Y,TNF一a and IL一4 seeretion in cell eultt犷e suPem的ants ofthePoxso.199 T cell and in blood sera ofthe户L1'- EAN ofall the grouPs.Both incell cultore suPem川别ats and in blood sera of all the grouPs comParing thenegative eontrOI,Thl cells seereting more IFN一and TNF一a and ThZ eellssec威ing less IL·4.CoeultL甘e of T eells with IL·12 enhaneed the seeretionof IFN一下,but not TNF一a,场七ereas eoeul奴甘e with IL一1 8 enhancedtheseeretion of INF一a.认七measure sPlenic eells of the quantities andpereentage of CD4+and cDS十T cells of each脚即using FACS andfind that IL·12脚即have a little more quantities of both CD4+andens十T cells,while IL一15脚即。川y have little increasing of en4+。IL一12/IL一15脚即nave 51如五eantly inereasing of both eD4+andeDs十T eells.only the IL一12/IL·15脚即shows a 51酗五eantly inerease吉林大学博士学位论文英文摘要些of the pereentage of CD4+/C DS+co哪如ng to the non一st如ulatedPO一50.199 gro即· Our stUdy sllggest that IL一1 Zts改esP斌in the inunun0Pal五ogenesisof AT-EAN bye川laneing the seeretion of IFN一丫while IL一18 takes Partin the im一nunoPathogenesis of AT-EAN by enhancing the seeretion of丁NF一a.IL一12 and IL一18 have signifieant synergetic effeet in Al'- EAN,mostly by the means of seereting large amount of IFN·丫.