The vertebrate immune system defends the organism against invading
pathogens while at the same time being self-tolerant to the body's
own constituentsthuspreservingitsintegrity.
Multiplemechanismsactinconcert to ensure self-tolerance. During
intrathymic development, the nascent T cell repertoire is purged
from autoreactive T cells via negative selection, a process also
known as recessive tolerance. Ridding of self-reactivity,
however,isnotcomplete,asattestedbythepresenceofself-reactiveTcells
intheperipheralTcellrepertoire.
Hence,additionaltolerancemechanisms, collectively referred to as
dominant tolerance, have been postulated on
theoreticalgrounds(seethechapterbyA. Coutinhoetal. inthisvolume)and
experimentalprooffortheirexistencehadbeenrepeatedlyclaimedinthepast
40years. Whilesomeoftheseclaims,largelybasedoninvitroexperiments,
laterfellintodisrepute(i. e.
,theinfamousCD8suppressorcellsexpressingI-J
molecules),concurrent,butlesswellpublicizedstringsofresearch,provided
unremitting evidence for dominant tolerance mechanisms. These
include the postnatal thymectomy model pioneered by Nishizuka and
Sakakura in 1969, the dominant tolerance model in chicken and quail
chimeras
introducedbyleDouarinandcolleagues,andstudiesoninfectioustolerance
by the Waldmann laboratory. A breakthrough in this ?eld was
achieved by the identi?cation and isolation by Sakaguchi's and
Shevach's groups of + + aCD4 CD25
TcellsubsetexertingsuppressiononeffectorTcellsbothin
vitroandinvivo. Thisinstigatedanavalancheofpublicationsonsuppressor
Tcells. Whilelargelyoverlookedforsomanyyears,thereisnowhardlyany
aspectofimmunitythatdoesnotseemtobeaffectedbysuppressorTcells. This
volume will hardly be more than a snapshot in thisfast-moving ?eld,
yetwehopethatitwillofferinspirationandorientationtothescientistwho
wouldliketoenterthis?eld. To date, many different cells have been
described that can suppress + + other cells of the immune system:
CD4 CD25 regulatory T cells (Treg), + ? CD4 CD25 regulatory T
cells, T regulatory 1 cells (Tr1), T-helper 3 cells + ? (Th3),CD8
CD28 Tcells,NKTcells,aswellastolerogenicdendriticcells. Suppressive
CD4 T cells fall at least into two categories. So called natural VI
Preface + + CD4 CD25
Tregformpartoftheintra-thymicallyselectedTcellrepertoire
andapparentlyconstituteadistinctlineage.
Incontrast,"adaptive"regulatory
Tcellsareinstructedintheperipherytobecomesuppressivecells,theyform
+ + amoreheterogeneousgroupincludingCD4 CD25 Treg,Tr1,andTh3cells.
As natural Treg are so far the best characterized entity, the ?rst
three contributionsofthisvolume(C. Cozzoetal. ,C. -S. Hsiehetal.
,andL.
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