Skip Navigation



Brain Advance Access published online on February 25, 2004
Brain, doi:10.1093/brain/awh119
© 2004 by Guarantors of Brain
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
127/5/981    most recent
awh119v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Laplaud, D.-A.
Right arrow Articles by Soulillou, J.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laplaud, D.-A.
Right arrow Articles by Soulillou, J.-P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2004 The Guarantors of Brain

Article

Blood T-cell receptor {beta} chain transcriptome in multiple sclerosis. Characterization of the T cells with altered CDR3 length distribution

David-Axel Laplaud 1, Catherine Ruiz 2, Sandrine Wiertlewski 3, Sophie Brouard 2, Laureline Berthelot 2, Marina Guillet 4, Benoît Melchior 2, Nicolas Degauque 2, Gilles Edan 5, Philippe Brachet 2, Philippe Damier 1, and Jean-Paul Soulillou 6*

1 Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 437: ‘Immunointervention dans les Allo- et Xénotransplantations’, Institut de Transplantation et de Recherche en Transplantation (ITERT), CHU Hôtel Dieu, 30 Bd Jean Monnet,C, 44093 Nantes Cedex 01, France; Clinique Neurologique and Centre d’Investigation Clinique, Hôpital G. et R. Laennec, Bd J. Monod, 44093 Nantes Cedex 01, France
2 Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 437: ‘Immunointervention dans les Allo- et Xénotransplantations’, Institut de Transplantation et de Recherche en Transplantation (ITERT), CHU Hôtel Dieu, 30 Bd Jean Monnet,C, 44093 Nantes Cedex 01, France
3 Clinique Neurologique and Centre d’Investigation Clinique, Hôpital G. et R. Laennec, Bd J. Monod, 44093 Nantes Cedex 01, France
4 TcLand S.A., 30 Bd Jean Monnet, 44093 Nantes Cedex 01, France
5 Service de Neurologie, Hôpital Pontchaillou, 35000, Rennes, France
6 Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 437: ‘Immunointervention dans les Allo- et Xénotransplantations’, Institut de Transplantation et de Recherche en Transplantation (ITERT), CHU Hôtel Dieu, 30 Bd Jean Monnet,C, 44093 Nantes Cedex 01, France; INSERM U437, 30 Bd Jean-Monnet, 44093 Nantes Cedex 01, France

* Corresponding author. E-mail: jps{at}nantes.inserm.fr.

Received 1 October 2003 ; revised 10 December 2003 ; accepted 14 December 2003

Abstract

Multiple sclerosis is an inflammatory demyelinating disease of the CNS associated with T cells autoreactive for myelin components. In this study, we analysed the T-cell receptor (TCR) usage of the variable {beta} (V{beta}) chain transcriptome in the blood of multiple sclerosis patients at various stages of the disease using a global and quantitative comparison of the complementarity-determining region 3 length distribution (CDR3-LD) of transcripts of the 26 V{beta} genes. We investigated 35 patients: 12 with a high risk of multiple sclerosis, 10 with clinically definite multiple sclerosis, 13 with a relapsing-remitting worsening and active multiple sclerosis and 13 healthy individuals. Cells bearing the TCR transcripts with altered CDR3-LD were sorted and studied for CD4 or CD8 phenotype, cytokine transcript accumulation and response to human myelin basic protein (MBP). We show that patients from all the groups have a significantly skewed blood T-cell repertoire. V{beta} transcriptome patterns were more altered in patients from the clinically definite multiple sclerosis group and the worsening and active multiple sclerosis group than in the high risk group. The T cells sorted from V{beta} families with altered CDR3-LD concerned both CD4 and CD8 T cells, with a more pronounced skewing in the CD8 compartment. These cells displayed a significantly increased level of interferon-{gamma}, interleukin-2 and tumour necrosis factor-{alpha} transcripts compared with their counterparts from the healthy individual group. Furthermore, using interferon-{gamma} enzyme-linked immunospot (ELISPOT) assays, T cells from four out of seven altered V{beta} families tested from multiple sclerosis patients responded to human MBP, whereas no response was observed with human albumin or with altered V{beta} families from healthy individuals. Our data support the concept of an early autoimmune component in the disease and emphasize the possible involvement of CD8-positive T cells in multiple sclerosis.

Keywords: CD4/CD8; CDR3; cytokines; multiple sclerosis; T cells; V{beta} genes
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 NeuroscientistHome page
S. Markovic-Plese
Degenerate T-Cell Receptor Recognition, Autoreactive Cells, and the Autoimmune Response in Multiple Sclerosis
Neuroscientist, June 1, 2009; 15(3): 225 - 231.
[Abstract] [PDF]

Home page
 BrainHome page
S.-Y. Na, Y. Cao, C. Toben, L. Nitschke, C. Stadelmann, R. Gold, A. Schimpl, and T. Hunig
Naive CD8 T-cells initiate spontaneous autoimmunity to a sequestered model antigen of the central nervous system
Brain, September 1, 2008; 131(9): 2353 - 2365.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
A. Junker, J. Ivanidze, J. Malotka, I. Eiglmeier, H. Lassmann, H. Wekerle, E. Meinl, R. Hohlfeld, and K. Dornmair
Multiple sclerosis: T-cell receptor expression in distinct brain regions
Brain, November 1, 2007; 130(11): 2789 - 2799.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
P. Somma, G. Ristori, L. Battistini, S. Cannoni, G. Borsellino, A. Diamantini, M. Salvetti, R. Sorrentino, and M. T. Fiorillo
Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis
J. Leukoc. Biol., March 1, 2007; 81(3): 696 - 710.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Brisebois, S. P. Zehntner, J. Estrada, T. Owens, and S. Fournier
A Pathogenic Role for CD8+ T Cells in a Spontaneous Model of Demyelinating Disease
J. Immunol., August 15, 2006; 177(4): 2403 - 2411.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. E. Albers, C. Visus, T. Tsukishiro, R. L. Ferris, W. Gooding, T. L. Whiteside, and A. B. De Leo
Alterations in the T-Cell Receptor Variable {beta} Gene-Restricted Profile of CD8+ T Lymphocytes in the Peripheral Circulation of Patients with Squamous Cell Carcinoma of the Head and Neck
Clin. Cancer Res., April 15, 2006; 12(8): 2394 - 2403.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. A. Friese and L. Fugger
Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?
Brain, August 1, 2005; 128(8): 1747 - 1763.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.