Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR) and NKG2D英文文献资料.docVIP
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Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR) and NKG2D英文文献资料
ClinicalDevelopmentalImmunology,June–December2006;13(2–4):325–336
Antigenpresentingcellsandstromalcellstriggerhumannaturalkiller
lymphocytestoautoreactivity:Evidencefortheinvolvementofnatural
cytotoxicityreceptors(NCR)andNKG2D
ALESSANDROPOGGI1MARIARAFFAELLAZOCCHI2
1NationalInstituteforCancerResearch,16132Genoa,Italy,and 2SanRaffaeleScienti?cInstitute,20132Milan,Italy
Abstract
Humannaturalkiller(NK)lymphocytesshouldnotdamageautologouscellsduetotheengagementofinhibitoryreceptor
superfamily(IRS)membersbyHLA-I.Nevertheless,NKcellskillselfcellsexpressinglowlevelsorlackingHLA-I,asitmay
occurduringviralinfections(missing-selfhypothesis).Herein,weshowthathumanNKcellscanbeactivateduponbinding
withselfantigenpresentingcellsorstromalcellsdespitetheexpressionofHLA-I.Indeed,NKcellscankillandproducepro-
in?ammatoryandregulatingcytokinesasIFN-g,TNF-aandIL10duringinteractionwithautologousdendriticcellsorbone
marrowstromalcellsorskin?broblasts.ThekillingofantigenpresentingandstromalcellsisdependentonLFA1/ICAM1
interaction.Further,thenaturalcytotoxicityreceptors(NCR)NKp30andNKp46areresponsibleforthedeliveryoflethalhit
toDC,whereasNKG2Dactivatingreceptor,theligandoftheMHC-relatedmoleculeMIC-AandtheUL16bindingprotein,
isinvolvedinstromalcellkilling.These?ndingsindicatethatdifferentactivating receptors areinvolvedincelltoselfcell
interaction.Finally,NKcellscanrevertthevetoeffectofstromalcellsonmixedlymphocytereactionfurthersupportingthe
ideathatNKcellsmayaltertheinteractionbetweenTlymphocytesandmicroenvironmentleadingtoautoreactivity.
Keywords: Naturalkillerlymphocyte,inhibitoryreceptorsuperfamily,HLA-I,TNF-a
Introduction
concentration of ligand (as it happens for self-
antigens)canresultintolerance;further,theabsence
of co-stimulatory signals may impair lymphocyte
responsetoself-ligands.Inthesetolerizingprocesses,
as well as during adaptive immune response against
non-self antigens the innate arm of the immune
systemplayakeyrole(Janaway1992).Dendriticcells
(DC)thatareco
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