Dendritic Cells

357 Pages·2009·7.089 MB·English

by  Sandra S. Diebold (auth.), Giovanna Lombardi, Yanira Riffo-Vasquez (eds.)

Handbook of Experimental Pharmacology
Volume 188
Editor-in-Chief
F.Hofmann,München
EditorialBoard
J.Beavo,Seattle,WA
A.Busch,Berlin
D.Ganten,Berlin
J.-A.Karlsson,Singapore
M.Michel,Amsterdam
C.P.Page,London
W.Rosenthal,Berlin
Giovanna Lombardi • Yanira Riffo-Vasquez
Editors
Dendritic Cells
Contributors
L.Adorini,W.vandenAncker,G.Belz,A.Benlahrech,F.Belardelli,M.Buckland,
A.E.Castell-Rodriguez, G.D’Agostino, S.S.Diebold, M.Ferrantini, R. Fischer,
K.A.Gelderman, H. Hammad, W. Han, M. Herrera-Enriquez, I. Houtenbos,
D. Kahler, A.KleinJan, C.vanKooten, B.N. Lambrecht, A. Lanzavecchia,
C.Lapenta,G.Lombardi,A.A.vandeLoosdrecht,A.Martín-Fontecha,F.Masson,
A.L.Mellor,A.Mount,G.J.Ossenkoppele,T.Papagatsias,S.Patterson,G.Penna,
T.R.D.J. Radstake, M.D. Ramirez-Gonzalez, F. Sallusto, S.M.Santini,
L.Santodonato,A.S.Stax,T.Taner,A.W.Thomson,H.R.Turnquist,R.E.M.Toes,
Y.R. Vasquez, L.G. Villanueva-Rodriguez, M.H. Wenink, T.M. Westers,
A.M.Woltman
123
Editors
GiovannaLombardi YaniraRiffoVasquez
ProfessorofHumanTransplantImmunology ResearchFellow
MRCCentreinTransplantation TheSacklerInstituteofPulmonary
Dep.ofNephrologyandTransplantation, Pharmacology
DIIID PharmaceuticalScienceDivision
King’sCollegeLondon 5thFloorHodgkinBuilding
SchoolofMedicine School of Biomedical and Health Sciences
Guy’sHospital King’sCollegeLondon
London,UK LondonSE11UL
[email protected] UnitedKingdom
[email protected]
ISBN978-3-540-71028-8 e-ISBN978-3-540-71029-5
HandbookofExperimentalPharmacologyISSN0171-2004
LibraryofCongressControlNumber: 2008932233
(cid:2)c Springer-VerlagBerlinHeidelberg 2009
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Preface
The understanding of the role of dendritic cells (DCs) in immune responses has
comealongwaysinceSteinmannandcolleaguesdescribedthesecellsin1972.Ex-
tensive research during the intervening period has provided a good understanding
ofthecomplexityoftheDCsystemanditspivotalroleinimmunity.Itisalsonow
clearerhowdifferentsubsetsofDCsinteractandregulateeachotherandhowDC
populationsaffectthefunctionofothercellsoftheimmunesystem.Theimproved
understandingoftheirroleinimmuneresponsehasledtotheideathatmodulation
ofDCfunctionsby,forexample,pharmacologicalagentscouldbeusedasapoten-
tialtherapeutic approach in some pathological conditions. The actual applicability
andtherapeuticpotentialofalltheseapproachesisyettobefullydemonstratedbut
nonetheless,animalmodelsofhumandiseasesareprovingtobeveryhelpfulinthe
evaluationofmanipulatedDCsasanewtreatmentindiseaseslikecancer,autoim-
munityorasthma.
DCsareintegraltotheinitiationandregulationofimmuneresponse(Banchereau
et al. 2000). The outcome of antigen presentation by DCs is determined by their
maturation status, which can be induced by their interaction with danger signals.
Torecogniseawidearrayofpathogen-associatedmolecularpatterns(PAMP),DCs
express a number of pattern recognition receptors (PRR) such as Toll-like recep-
tors(TLRs)andC-typelectinreceptors(CLR)thatrecognisestructuralcomponents
of pathogens and discriminate between self and non-self molecules. The distribu-
tion of PRRs by DCs is variable and differs between DC subsets, as reviewed in
this issue of Handbook of Experimental Pharmacology. Following an encounter
with pathogens, DCs stop sampling the microenviroment and became dedicated
antigen presenting cells. These mature DCs migrate to the secondary lymphoid
organs and present antigen to lymphocytes. The trafficking of DCs, in particu-
lar from skin and blood, has been reviewed in this volume. Mature DCs have a
potent capacity to stimulate T cells, while immature DCs fail to fully activate T
cellsandcaninduceTcelltolerancethroughanergy,deletionorinductionofTregs
(Bonifaz et al. 2002; Hawiger et al. 2001). More specifically, different DC sub-
sets appear to have distinct effects on T cell behaviour. DCs are in fact a very
heterogenous population of cells. In mice there are at least six major subtypes of
v
vi Preface
DCs (reviewed by Pulendran et al. 2008). In the spleen and lymph nodes, DCs
are characterised by the expression of CD11c and MHC class II. In the spleen
there are three subsets: (1) CD11chighCD8α+CD11b−DEC205+ (CD8α+ lym-
phoid DCs); (2) CD11chighCD8α−CD11b+DEC205− (CD8α− myeloid DCs); (3)
CD11cintCD8α+/−CD11b+B220+Gr-1+− (pDCs). However there is another way
in which splenic DCs have been classified, based on the expression of CD4 and
CD8 surface markers (Dudziak et al. 2007; Masson et al. 2008). Using these two
markers, three populations of DCs can be discerned in the spleen: CD8α+CD4−
(CD8αDCs)CD8α−CD4+,andCD8α−CD4− (thelasttwodefinedasnonCD8α
DCs).Furthermore,theCD8α+CD4− DCsexpresstheCD205molecule,whilethe
CD8α−CD4+ DCs express a high level of the C-type lectin inhibitory receptor-2
(DCIR2) which can be targeted by the antibody 33D1 (Dudziak et al. 2007).
The percentages vary slightly, depending on the mouse strain. More recently, it
has been shown that CD4−CD8α+ and CD4+CD8α− DC stimulate CD8+ and
CD4+ T cells respectively (Dudziak et al. 2007). These properties are related
to differences in the MHC class I and MHC class II antigen presentation path-
ways (Dudziak et al. 2007). In the lymph nodes there are two additional subsets
CD11chighCD8αdullDEC205highLangerin+ (Langherans cell-derived DCs-LCDCs)
andCD11chighCD8α−CD11b+DEC205+ (DermalDCs).TheLCDCsandtheDer-
mal DCs in the lymph nodes are derived from skin (reviewed in this volume). All
these subsets of DCs have different locations in the secondary lymphoid organs.
TheCD11chighCD8α+ DCsarelocalisedintheTcellareawhiletheCD8α− DCs
are localised in the marginal zones of the spleen and the subcapsular sinuses of
thelymphnodes.TheCD8α+ DCsubsetsecreteIL-12whiletheCD8α− produce
mostly IL-10. While in vivo data suggests that CD8α+ DC stimulation of T cells
generallypromotesTh1andCD8α− DCsmainlypromoteaTh2response,invitro
stimulation has shown that this division can be overcome (Maldonado-Lopez and
Moser2001).Inthisissuetheroleinparticularoftheanti-viralimmuneresponsesof
differentDCssubsetswillbediscussed.ApartfromthethreesubsetsofDCspresent
intheskin(LCDCs,DermalDCsandpDCs)thatmigratetothelymphnodesfollow-
ingactivation,fourdifferentsubsetsofDCshavebeendescribedinthreemainloca-
tionsintheintestine(Peyer’spatches,laminapropria,andmesentericLNs).These
four subsets are similar to the subsets identified in the spleen with an additional
marker,CCR6,tosubdividetheCD11cbrightCD8α−CD11b+DCs.Veryrecentlyan
alternative classification of DC subsets has been used, based on the expression of
chemokinereceptorCX3CR1andCD103,furtherconfirmingtheunresolvedissue
ofDCsubsetsinthemouse.
PlasmacytoidDCsareaspecialisedDCsubsetofdistinctlineagefromCD11chigh
DCs, and they produce type I IFNs in response to microbial infections. Immature
pDCsarepoorstimulatorsofna¨ıveTcellactivation,aconsequenceoftheirlowex-
pressionlevelsofco-stimulatorymoleculesandintermediateMHCclassIIexpres-
sion (Martin et al. 2002), (Asselin-Paturel et al. 2001). As applies to conventional
CD11chigh DCs,thematurationstatusofthepDCdeterminesitsstimulatorypoten-
tial,anduponmaturation,pDCsacquiretheabilitytoprimeTcellresponses,albeit
less than CD11chigh DCs (Salio et al. 2004). Although pDCs have a key role in a
Preface vii
number of immune-mediated diseases such as psoriasis and immunity to tumours
and pathogens, pDCs have also the ability to down-regulate the immune response
(Abeetal.2005;Mosemanetal.2004;Ochandoetal.2006).AspectsofpDCmi-
grationandfunctionarediscussedinthisbook.
In humans there are two major DC subtypes described, classically defined as
MyeloidandLymphoid.MyeloidDCsaredividedintosteadystateDCs,including
LangheranscellsandInterstitialDCsthatcontinuallysamplethemicroenviroment,
and inflammatory DCs that are generated in response to inflammation (Shortman
and Naik 2007). The other prominent DC subtype in the human is the type-I IFN
producingpDCs,thatrespondtoviralinfection(14).DCscanbegeneratedinvitro
fromCD14+CD11c+monocytewithGranulocyte/MacrophageColony-Stimulating
Factor(GM-CSF)andIL-4(SallustoandLanzavecchia 1994).Alternativelyithas
been shown that the addition of type-I IFN or TGF-β and GM-CSF can result
in DCs deficient in the adhesion molecule DC-SIGN that resembles Langherans
cells (Relloso et al. 2002). Human Myeloid DCs can also be directly obtained ex
vivofromthebloodbyusinganantibodythatrecognisestheBloodDendriticCell
Antigen-2 (BDCA-2+) marker. Plasmacytoid DCs can also be generated ex vivo
fromBDCA-4+precursorandculturedinthepresenceofIL-3(Itoetal.2007).
Altogether the overview of the DC subsets presented here further highlights
the complexity of the DC system and raises important questions about the use of
DCs in immunotherapy. The growing importance of DCs in the immune system
is confirmed by the ever increasing number of published data found in the litera-
ture. We felt it timely to commission a contemporary review of the current under-
standingofDCfunctioninhealthanddiseaseandtheirpotentialmanipulationfor
immunotherapy.
Inthefirstpartofthisvolume,theauthorspresentaverycomprehensivereview
ofDCsaspivotalcomponentsoftheimmunesystem,asalreadymentioned.Inthe
threeinitialchapterswewilllearnwhatiscurrentlyknownaboutactivation,migra-
tion, and function of DCs as antigen presenting cells and T-cell activators. These
chapterslaythefoundationforthesecondpartofthisvolume,whichdescribesthe
role of DCs in diseases. It is clear that DCs are important in many pathological
conditions.However,itwouldhavebeenverydifficulttodiscussalloftheminone
singlevolume.Wehavechosensomeconditionswheresignificantresearchhasbeen
done in the last few years and where DCs have been shown to be a potential ther-
apeutictarget(RheumatoidArthritis,AllergicDiseasesandDrugInducedAdverse
Reaction).
In the last part of the volume we take a closer look at the current status of the
specific use of DCs as therapy. The first chapter discusses the intrinsic properties
of a subpopulation of pDCs that express IDO following inflammatory conditions
andtheircriticalroleasregulatoroftheimmuneresponse.Thechapterfinishesby
reviewingtheopportunitytomanipulateIDOexpressioninDCsforimmunotherapy.
This review is followed by four chapters where the authors discuss the manipula-
tionofDCstoinducetoleranceintransplantationandautoimmunity,usingvarious
drugs(Aspirin,Rapamycin,DexamethasoneandVitaminDReceptorAntagonists).
ThelastthreechaptersreviewthegeneralknowledgeontheuseofDCstobooster
viii Preface
theimmuneresponsesinthetreatmentofviralinfections,cancerandinparticular,
leukaemia.ThefirstchapterfocusesonthedevelopmentofHIVvaccinesbasedon
recombinant adenoviruses (rAd). This review discusses the different types of rAd
vectors and their effect in stimulating the DCs and the other cells of the immune
system. This chapter is followed by a review of our knowledge of the role played
bytypeIIFNsinthedifferentiationandactivationofDCstowardstheprimingand
expansion of protective antitumour responses. The chapter finishes by discussing
how the type I IFNs could be exploited to develop strategies for an effective can-
cerimmunotherapy.Finally,thelastchapterdiscussestheuseofDCvaccinationto
overcomethe“intrinsictolerantstate”ofpatientswithacutemyloidleukaemia.The
authorsalsomentionthepossibilityofusinganAML-derivedcellline(MUTZ-3),
equivalenttoCD34+DCprecursorcells,forvaccinationpurpose.
Altogether, the genetic or pharmacological manipulations of DCs and their po-
tential use in vaccination have raised expectation and hopes in many areas of re-
search concerning the induction of tolerance in autoimmunity and transplantation
and the stimulation of the immune responses in cancer and viral infections such
as HIV. A great deal of data derived from animal models of human diseases have
been published in the last few years from leading laboratories around the world,
suggestingthatthistypeoftreatmentisarealpossibilityintheverynearfuture.
Wehopethatthisbookwillgivethereaderabetterunderstandingofthebiology
ofDCsandwhythesecellsaresuchimportantplayersinthebattleagainstdiseases.
We thank our contributors who, with great professionalism, have shared their
knowledgeandexpertisewithus.
London,UnitedKingdom GiovannaLombardi
YaniraVasquez
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Contents
PartI BiologyofDendriticCells
ActivationofDendriticCellsbyToll-LikeReceptors
andC-TypeLectins.............................................. 3
SandraS.Diebold
DendriticCellMigrationtoPeripheralLymphNodes ................. 31
AlfonsoMart´ın-Fontecha,AntonioLanzavecchia,andFedericaSallusto
DendriticCellsinViralInfections.................................. 51
GabrielleBelz,AdeleMount,andFrederickMasson
PartII RoleofDendriticCellsinDisease
Dendritic Cells and their Potential Implication in Pathology
andTreatmentofRheumatoidArthritis............................. 81
M.H.Wenink,W.Han,R.E.M.Toes,andT.R.D.J.Radstake
LungDendriticCells:TargetsforTherapyinAllergicDisease .......... 99
BartN.LambrechtandHamidaHammad
DendriticCellsinRhinitis ........................................ 115
AlexKleinJanandBartN.Lambrecht
Role of Epidermal Dendritic Cells in Drug-Induced Cutaneous
AdverseReactions............................................... 137
Maria Dolores Ramirez-Gonzalez, Miguel Herrera-Enr´ıquez,
LuisaGeraldineVillanueva-Rodr´ıguez,andAndre´sEliuCastell-Rodr´ıguez
xi
xii Contents
PartIII ManipulationofDendriticCellsforImmunotherapy
TCellRegulatoryPlasmacytoidDendriticCellsExpressingIndoleamine
2,3Dioxygenase................................................. 165
DavidJ.KahlerandAndrewL.Mellor
AspirinandtheInductionofTolerancebyDendriticCells ............. 197
MatthewBucklandandGiovannaLombardi
UseofRapamycinintheInductionofTolerogenicDendriticCells....... 215
RyanFischer,HethR.Turnquist,Timuc¸inTaner,andAngusW.Thomson
HandbookofExperimentalPharmacology“DendriticCells” ........... 233
Cees van Kooten, Annelein S. Stax, Andrea M. Woltman,
andKyraA.Gelderman
InductionofTolerogenicDendriticCellsbyVitaminD
ReceptorAgonists............................................... 251
LucianoAdoriniandGiuseppePenna
UseofAdenovirusinVaccinesforHIV ............................. 275
StevenPatterson,TimosPapagatsias,andAdelBenlahrech
IFN-alpha in the Generation of Dendritic Cells
forCancerImmunotherapy....................................... 295
Stefano Maria Santini, Caterina Lapenta, Laura Santodonato,
GiuseppinaD’Agostino,FilippoBelardelli,andMariaFerrantini
Dendritic Cell-Based Immunotherapy in Myeloid Leukaemia:
TranslatingFundamentalMechanismsintoClinicalApplications ....... 319
A.A. van de Loosdrecht, W. van den Ancker, I. Houtenbos,
G.J.Ossenkoppele,andT.M.Westers
Index .............................................................349