Functionally Suppressive CD8 T Regulatory Cells Are Increased in Patients with Multiple Myeloma A Cause for Immune Impairment 英文参考文献.docVIP

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Functionally Suppressive CD8 T Regulatory Cells Are Increased in Patients with Multiple Myeloma A Cause for Immune Impairment 英文参考文献.doc

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Functionally Suppressive CD8 T Regulatory Cells Are Increased in Patients with Multiple Myeloma A Cause for Immune Impairment 英文参考文献

FunctionallySuppressiveCD8TRegulatoryCellsAre IncreasedinPatientswithMultipleMyeloma:ACausefor ImmuneImpairment KarthickRajaMuthuRaja1,2*,LenkaKubiczkova1,LucieRihova1,3,MartinPiskacek1,PavlaVsianska2,3, RenataHezova5,LudekPour4,RomanHajek1,2,3,4 1BabakMyelomaGroup,DepartmentofPathologicalPhysiology,FacultyofMedicine,MasarykUniversity,Brno,CzechRepublic,2DepartmentofExperimentalBiology, FacultyofScience,MasarykUniversity,Brno,CzechRepublic,3DepartmentofClinicalHematology,UniversityHospital,Brno,CzechRepublic,4DepartmentofInternal Medicine,Hemato-oncology,UniversityHospital,Brno,CzechRepublic,5CentralEuropeanInstituteofTechnology,MasarykUniversity,Brno,CzechRepublic Abstract Background:Multiplemyeloma(MM)isaplasmacellmalignancyfrequentlyassociatedwithimpairedimmunecellnumbers and functions. In MM, several studies have previously shown that CD4 regulatory T (Treg) cells hamper effector T cell functionsandenhanceimmunedysfunction.Inthisstudy,weaimedtoprovethepresenceoffunctionallysuppressiveTreg cellsexpressingCD8phenotype(CD8Tregcells)inMM.Tothebestofourknowledge,thishasnotbeenreportedpreviously inMM. Methods:WeanalyzedCD8TregcellsandtheirtranscriptionfactorFoxP3from64newlydiagnosedMMpatientsusingflow cytometryandrealtime-polymerasechainreaction(RT-PCR).RNAprofileofcytokinesinCD8Tregcellswasalsoassessed using RT-PCR. CD8 Treg cells from 5MM patients and 5 healthy donors were functionally evaluated using proliferation assays. Results:CD8Tregcells(CD8+CD25hi+)weresignificantlyelevatedinMMpatients(P,0.0001),andtheirtranscriptionfactor FoxP3expressionwasalsohigherinMM(P,0.0001)comparedtohealthydonorswhichwasevidencedbyflowcytometry and RT-PCR analyses. CD8 Treg cells negatively correlated with total lymphocyte count (P=0.016). Functional studies revealed that CD8 Treg cells isolated from MM patients and healthy donors inhibited proliferation of CD4 T cells in a concentrationdependentmanner.InthepresenceofCD8Tregcellsinproliferationassays,levelofIFN-cwasdecreasedbut not