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A phenotypic, transcriptional and TCR Vβ repertoire signature of CD8+ T cells define a population at-risk of long-term kidney graft dysfunction

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HAL Id: inserm-00758214

https://www.hal.inserm.fr/inserm-00758214

Submitted on 28 Nov 2012

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A phenotypic, transcriptional and TCR Vβ repertoire

signature of CD8+ T cells define a population at-risk of

long-term kidney graft dysfunction

Nicolas Degauque, Françoise Boeffard, Annaick Pallier, Richard Danger,

Magali Giral, Jacques Dantal, Yohann Foucher, Cécile Guillot-Gueguen,

Jean-Paul Soulillou, Sophie Brouard

To cite this version:

Nicolas Degauque, Françoise Boeffard, Annaick Pallier, Richard Danger, Magali Giral, et al.. A

phe-notypic, transcriptional and TCR Vβ repertoire signature of CD8+ T cells define a population at-risk

of long-term kidney graft dysfunction. 7th European Workshop on Immune-Mediated Inflammatory

Diseases, Nov 2012, Netherlands. pp.P59. �inserm-00758214�

(2)

P O S T E R P R E S E N T A T I O N

Open Access

A phenotypic, transcriptional and TCR V

b

repertoire signature of CD8+ T cells define a

population at-risk of long-term kidney graft

dysfunction

Nicolas Degauque

1,2,3*

, Françoise Boeffard

1,2,3

, Annaick Pallier

1,2,3

, Richard Danger

1,2,3

, Magali Giral

1,2,3

,

Jacques Dantal

1,2,3

, Yohann Foucher

2,4

, Cécile Guillot-Gueguen

2

, Jean-Paul Soulillou

1,2,3

, Sophie Brouard

1,2,3

From 7th European Workshop on Immune-Mediated Inflammatory Diseases

Noordwijk aan Zee, the Netherlands. 28-30 November 2012

Introduction

The biological mechanisms leading to chronic antibody-mediated rejection (CAMR), a major cause of late graft failure following kidney transplantation, are still poorly defined. Although anti-donor HLA antibodies are com-monly associated with poor graft outcome; less attention had been paid to other players of the adaptive immune system.

Aim

We took advantage of a large cohort of 133 selected patients (112 patients remaining stable in time and 21 with kidney dysfunction over 6 years) to question the fac-tors that may influence graft outcome.

Results

We show that T cell monitoring, and especially CD8 TCR repertoire alterations, may allow identifying patients at risk of graft dysfunction. As compared to patients without TCR Vb repertoire alterations, patients with an altered TCR Vb repertoire at the inclusion have a 2.1 fold higher risk of graft dysfunction during their follow-up. The Vb repertoire alteration occurs years before the appearance of de novo anti-HLA antibodies.

Moreover, these patients with an altered TCR repertoire exhibit an increase in effector memory CD45RA-CD197 -CD8+ T cells with an accumulation of differentiated (CD28low) CD8 T cells. Finally, a specific CD8 gene expression pattern composed of 92 genes related to CD8

T cell function and phenotype can discriminate these patients from patients with lesions of CAMR.

Conclusions

Monitoring the TCR Vb repertoire of circulating CD8 T cells may help to improve the identification of at-risk patients before the detection of HLA antibodies. Besides offering a new tool for monitoring patients, our data shed new light on the status of T cell immunity in long-term graft outcome.

Author details

1INSERM, UMR 1064, Nantes, France.2CHU de Nantes, ITUN, Nantes, France. 3Université de Nantes, Faculté de Médecine, Nantes, France.4Université de

Nantes, EA 4275, Nantes, France. Published: 28 November 2012

doi:10.1186/1479-5876-10-S3-P59

Cite this article as: Degauque et al.: A phenotypic, transcriptional and TCR Vb repertoire signature of CD8+ T cells define a population at-risk of long-term kidney graft dysfunction. Journal of Translational Medicine 2012 10(Suppl 3):P59.

1INSERM, UMR 1064, Nantes, France

Full list of author information is available at the end of the article

Degauque et al. Journal of Translational Medicine 2012, 10(Suppl 3):P59 http://www.translational-medicine.com/content/10/S3/P59

© 2012 Degauque et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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