Analysis of the peripheral T-cell repertoire in kidney transplant patients

被引:28
作者
Miqueu, Patrick [1 ,2 ,3 ]
Degauque, Nicolas [1 ]
Guillet, Marina [2 ]
Giral, Magali [1 ]
Ruiz, Catherine [2 ]
Pallier, Annaick [1 ]
Braudeau, Cecile [1 ]
Roussey-Kesler, Gwenaelle [1 ]
Ashton-Chess, Joanna [1 ,2 ]
Dore, Jean-Christophe [4 ]
Thervet, Eric [5 ,6 ]
Legendre, Christophe [5 ,6 ]
Hernandez-Fuentes, Maria P. [7 ]
Warrens, Anthony N. [8 ]
Goldman, Michel [9 ]
Volk, Hans-Dieter [10 ,11 ]
Janssen, Uwe [12 ]
Wood, Kathryn J. [13 ]
Lechler, Robert I. [7 ]
Bertrand, Dominique [14 ]
Sebille, Veronique [3 ]
Soulillou, Jean-Paul [1 ]
Brouard, Sophie [1 ]
机构
[1] Univ Nantes, CHU Nantes, Inst Transplantat & Rech Transplantat, Fac Med Nantes,RTRS Centaure,INSERM,U643, Nantes, France
[2] TcLand Express SA, Nantes, France
[3] Fac Pharm, Biostat Rech Clin & Mesures Subject Sante EA 4275, Nantes, France
[4] CNRS MNHN, UMR 5154, Paris, France
[5] Univ Paris 05, Paris, France
[6] Hop Necker Enfants Malad, AP HP, Paris, France
[7] Kings Coll London, Med Res Council Ctr Transplantat, Sch Med, Guys Hosp, London WC2R 2LS, England
[8] Univ London Imperial Coll Sci Technol & Med, London, England
[9] Univ Libre Bruxelles, Inst Med Immunol, Charleroi, Belgium
[10] Charite, Inst Med Immunol, D-13353 Berlin, Germany
[11] Charite, Berlin Brandenburg Ctr Regenerat Med, D-13353 Berlin, Germany
[12] Miltenyi Biotec GmbH, MACSmol Business Unit, Cologne, Germany
[13] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Transplantat Res Immunol Grp, Oxford OX3 9DU, England
[14] INRA BIA, Nantes, France
关键词
Bioinformatics; Graft rejection; T cells; TCR; Transplantation; TERM GRAFT-SURVIVAL; CHRONIC REJECTION; OPERATIONAL TOLERANCE; RECEPTOR USAGE; CYTOMEGALOVIRUS; RECIPIENTS; DONOR; FREQUENCY; ALLOGRAFT; VIRUS;
D O I
10.1002/eji.201040301
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+)/CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.
引用
收藏
页码:3280 / 3290
页数:11
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