The Journal of Experimental Medicine
o.22 o ,Nvme ,20 2312 www.jem.org/cgi/doi/10.1084/jem.20051135 1213–1223 November7,2005 Vol. 202,No. 9, E h okfle nvriyPes$8.00 JEM ©TheRockefeller University Press thymic stromallymphopoietin. TLR, Toll-likereceptor;TSLP, DC; OX40L,OX40ligand; CD40 ligand;mDC,myeloid APC, allophycocyanin;CD40L, Abbreviations usedinthispaper: [email protected] Yong-Jun Liu: CORRESPONDENCE
Zhengbin Yao, Guy J. Delespesse, The onlineversionof thisarticlecontainssupplementalmaterial. T. ItoandY.-H.Wangcontributedequally tothiswork. (TSLP) primenaiveCD4 We recentlyshowedthatdendriticcells(DCs)activatedbythymicstromallymphopoietin 5 4 3 1 Tomoki Ito, response through OX40 ligand an inflammatory T helpertype2cell TSLP-activated cellsinduce dendritic Thus, itisdifficultconceptually andexperimen- and -13aredefinedasantiinflammatory (12). flammatory, Th2cellsthatproduce IL-4,-5,-10, IFN- tolerance (10,11).Third,historically,although cause allergicinflammation,butratherinduce been usedtoprimeTh2cellresponsesdonot models, lowaffinity–alteredpeptidesthathave allergic inflammation(6–9).Second,inanimal studies havedemonstratedthatIL-10suppresses in eitherhumansormice(3–5);fact,many appear tocontributeallergicinflammation in allergicinflammation.First,IL-10doesnot cells thatseemtoprecludetheirinvolvement there arecharacteristicsofconventionalTh2 gic tracellular parasiticinfectionandofaller- development ofantibodyresponsesagainstex- -10, tor TcellswiththecapacitytoproduceIL-4,-5, CD4
regulatory ThcellresponsesintoTNF- cell polarizationintheabsenceofIL-12,andproposethatOX40LcanswitchIL-10–producing Tanox, Inc.,Houston,TX77025 Allergy ResearchLaboratory, ResearchCenterofCentreHospitalierUniversitédeMontreal,NotreDameHospital, Department ofHematology/Oncology, GraduateSchoolofMedicine,KyotoUniversity, Sakyo-ku,Kyoto606-8507, Japan Center forCancerImmunologyResearch,DepartmentofImmunology, TheUniversityofTexas M.D.AndersonCancerCenter, Quebec H2L4M1,Canada and
produced highamountsoftumornecrosisfactor-
TNF- IL-12; and(c)OX40LexacerbatedIL-12–inducedTh1cellinflammationbypromoting in developingTh2cells;(b)OX40Llosttheabilitytopolarizecellspresenceof
IL-12. TSLP-inducedOX40LonDCswasrequiredfortriggeringnaiveCD4 Here wereportthatTSLPinducedhumanDCstoexpressOX40ligand(OX40L)butnot
properties ofOX40L:(a)OX40LselectivelypromotedTNF- produce IL-4,-5,and-13.Wefurtherrevealedthefollowingthreenovelfunctional 2
immune
The UniversityofTexas GraduateSchoolofBiomedicalSciencesatHouston,TX77030 and -13(1,2).Th2cellsarecriticalforthe
Th2cellsarehistoricallydefinedaseffec- –producing Th1cellsaredefined asin-
, whileinhibitingIL-10.WeconcludethatOX40LonTSLP-activatedDCstriggersTh2
responses toallergens.However, 1 Yui-Hsi Wang, 5 Wei Cao, 4 Norihiko Norihiko Watanabe, Tcellstodifferentiateintohelpertype2(Th2)that 1 and Yong-Jun Liu 1 OmarDuramad, –producing inflammatoryThcellresponses. (TNF- els of ably, theseTh2cellsproduceveryhighlev- IL-4, -5,and-13,butnotIL-10(13).Remark- Th2 cellthatproducestheclassiccytokines inflam cell isinvolvedinthedevelopmentofallergic tally to tally to human CD4 tory chemicals, microbes, orallergensinitiallycause findings suggestthatallergic insultsfrom migration andactivationin situ (13).These pression isalsoassociatedwith Langerhanscell tinocytes ofatopicdermatitis (13).TSLPex- IL-10–producing Th2cells. flammation, incontrasttotheconventional the pathogenicTh2cellsthatcauseallergicin- TNF- like cytokine(13).Webelieve,therefore,these thymic stromallymphopoietin(TSLP),anIL-7– neic myeloidDCs(mDCs)activatedbyhuman 1 F. Xiao-Feng Qin, We recentlydescribedanewtypeofhuman We foundthatTSLPisexpressed bykera- (TNF- Th2 cellswereoriginallygeneratedfrom mation. TNF- 1,2 2 compre 2 1,2 IL-10 ), IL-10–negative(IL-10 Toshiyuki Hori, , butinhibitedIL-10production ), butnointerleukin(IL)-10. naiveTcellsculturedwithalloge- . TheseTNF- hend howantiinflammatoryTh2 Th2cellsmostlikelyrepresent 1