Skip Navigation



Brain Advance Access published online on August 18, 2006
Brain, doi:10.1093/brain/awl213
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
129/10/2635    most recent
awl213v2
awl213v1
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 Tischner, D.
Right arrow Articles by Reichardt, H. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tischner, D.
Right arrow Articles by Reichardt, H. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received April 7, 2006
Revised July 19, 2006

Article

Polyclonal expansion of regulatory T cells interferes with effector cell migration in a model of multiple sclerosis

Denise Tischner 1, Andreas Weishaupt 2, Jens van den Brandt 1, Nora Müller 1, Niklas Beyersdorf 1, Chi Wang Ip 2, Klaus V. Toyka 2, Thomas Hünig 1, Ralf Gold 3, Thomas Kerkau 1, and Holger M. Reichardt 1 *

1 Institute for Virology and Immunobiology, University of Würzburg, Germany
2 Department of Neurology, Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, University of Würzburg, Germany
3 Institute for Multiple Sclerosis Research, Medical Faculty and Gemeinnützige Hertie-Stiftung, University of Göttingen, Germany

* To whom correspondence should be addressed.
Holger M. Reichardt, E-mail: holger.reichardt{at}mail.uni-wuerzburg.de


  Abstract

Recruitment of naturally occurring CD4+ CD25+ regulatory T (Treg) cells is a highly promising approach for the treatment of experimental autoimmune encephalomyelitis (EAE), a widely used model of multiple sclerosis. Here, we studied the in vivo interaction of Treg cells, induced by the monoclonal anti-CD28 antibody JJ316, with encephalitogenic T cell lines established from eGFP-transgenic rats. By tracking these fluorescent cells using flow cytometry and confocal microscopy, we found that the activation and expansion of Treg cells inhibited infiltration of the CNS by pathogenic T cells. Interference with effector cell migration occured within the secondary lymphoid organs, since the early therapeutic effects were achieved despite the absence of Treg cells in the spinal cord. However, the delayed homing to the CNS seen after prophylactic JJ316 administration indicates that Treg cells may play an additional role within the target tissue. In addition, the blood-brain barrier remained largely intact after JJ316 treatment, the secretion of TH2 cytokines was augmented and the encephalitogenic T cells exhibited a reduced secretion of IFN-{gamma}. This in turn resulted in a reduced expression of the chemokine receptor CXCR-3 on effector T cells which may interfere with their capacity to infiltrate the CNS. Importantly, these effects were not achieved by direct action of JJ316 on the encephalitogenic cells. Our data rather suggest that polyclonal activation of Treg cells in the secondary lymphoid organs is instrumental in preventing the pathological transmigration of encephalitogenic T cells into the CNS. We anticipate that these results may help to better understand the role of Treg cells in controlling autoimmunity in the CNS.

Keywords: experimental autoimmune encephalomyelitis; immunotherapy; regulatory T cells; cell migration; CXCR-3.
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
 J. Immunol.Home page
Y. Wang, D. Feng, G. Liu, Q. Luo, Y. Xu, S. Lin, J. Fei, and L. Xu
{gamma}-Aminobutyric Acid Transporter 1 Negatively Regulates T Cell-Mediated Immune Responses and Ameliorates Autoimmune Inflammation in the CNS
J. Immunol., December 15, 2008; 181(12): 8226 - 8236.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. Beyersdorf, X. Ding, G. Blank, K. M. Dennehy, T. Kerkau, and T. Hunig
Protection from graft-versus-host disease with a novel B7 binding site-specific mouse anti-mouse CD28 monoclonal antibody
Blood, November 15, 2008; 112(10): 4328 - 4336.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H.-Y. Lim, J. van den Brandt, M. Fassnacht, B. Allolio, M. J. Herold, and H. M. Reichardt
Silencing of the Mineralocorticoid Receptor by Ribonucleic Acid Interference in Transgenic Rats Disrupts Endocrine Homeostasis
Mol. Endocrinol., June 1, 2008; 22(6): 1304 - 1311.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. G. Meuth, S. Bittner, P. Meuth, O. J. Simon, T. Budde, and H. Wiendl
TWIK-related Acid-sensitive K+ Channel 1 (TASK1) and TASK3 Critically Influence T Lymphocyte Effector Functions
J. Biol. Chem., May 23, 2008; 283(21): 14559 - 14570.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. D. Reynolds, R. Banerjee, J. Liu, H. E. Gendelman, and R. L. Mosley
Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease
J. Leukoc. Biol., November 1, 2007; 82(5): 1083 - 1094.
[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.