Medical Microbiology

thymushadbeenremoved(andwhichthereforehadnoTcells).Implantation

ofanewthymuswithMHCclassImoleculesoftypea(MHCclassIa)intothe

MHCclassIbmiceresultedinthematurationofTcellswhichonlyrecognized

peptidespresentedbyMHCclassIamolecules,andnotpeptidespresentedby

MHCclassIbmolecules.However,recentexperimentshaveshownthatthisis

probableanexperimentalartefactandthatitisnot(ornotsolely)thethymic

epithelialcellsthatdeterminetheselectionprocess,butthatthisprocessis

drivenbycellsformedinthebonemarrow.Positiveselectionisgenerally

achievedbyweaklevelsofbindingaffinitybetweentheT-cellreceptor

andtheself-MHCmolecules,whereasnegativeselectioneliminatesthose

Tcellsexhibitingthehighestlevelsofaffinity(namelytheself-orauto-reac-

tiveTcells)andabsenceofbindingcausesdeathbyneglect.Thus,onlyTcells

withmoderatebindingaffinitiesareallowedtomatureandexitthethymus.

TheseTcellscanpotentiallyreacttonon-self(foreign)peptidespresentedby

selfMHCmolecules.Theenormousproliferationofimmaturethymocytesis

paralleledbycontinuouscelldeathoflargenumbersofthymocytes(apop-

tosis,seesummaryinFig.2. 17 ,p.88).Ingeneral,thematurationandsurvival

oflymphocytesisconsideredtobedependentonacontinuous,repetitive,

signalingviatransmembranemolecules,andcessationofthesesignalsis

usuallytakenasareliableindicatorofcelldeath.

T-CellSubpopulations

Inordertorecognizethepresentedantigen,TcellsrequirethespecificT-cell

receptorandamoleculewhichfunctionstorecognizetheappropriateMHC

molecules(i.e.CD4orCD8whichrecognizeMHCclassIIandMHCclassI,

respectively).ThusTcellsareclassifiedintodifferentsubpopulationsbased

ontheCD4orCD8surfacemolecules:

CD4+Tcells.TheseTcellsrecognizeonlyMHCclassII-associatedantigens.

TheyarealsocalledThelpercellsduetotheirimportantroleinT-Bcellcol-

laboration(Fig.2.9a),althoughtheyexhibitmanyotheradditionalfunctions.

CD4+cellscanproduce,orinduce,theproductionofcytokinesbywhich

meanstheycanactivatemacrophagesandexercisearegulatoryeffecton

otherlymphocytes(seep.75f.).Althoughthesecellssometimesdemonstrate

anabilitytocausecytotoxicdestructioninvitro,thisdoesnotholdtruein

vivo.

CD8+Tcells.OnlyMHCclassI-associatedantigensarerecognizedbythe

CD8+molecule.ThesecellsarealsoknownascytotoxicTcellsduetotheir

abilitytodestroyhistocompatiblevirus-infected,orotherwisealtered,target

cellsaswellasallogeneiccells.Thiseffectcanbeobservedbothinvitroand

invivo(Fig.2.9b).Costimulatorymoleculesarenotrequiredforthislytic

64 2 BasicPrinciplesofImmunology

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Kayser, Medical Microbiology © 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license.