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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.
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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