Document Detail


Regulatory T cells play a role in T-cell receptor CDR2 peptide regulation of experimental autoimmune encephalomyelitis.
MedLine Citation:
PMID:  22044096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Eliciting T-cell receptor (TCR) -specific responsiveness has been known to provide an effective autoregulatory mechanism for limiting inflammation mediated by T effector cells. Our previous use of TCR peptides derived from the CDR3 regions of a pathogenic TCR effectively reversed ongoing experimental autoimmune encephalomyelitis (EAE) in a humanized TCR transgenic model. In this study, we use the TCR BV8S2 CDR2 peptide in the non-transgenic C57BL/6 EAE model to down-regulate the heterogeneous TCR BV8S2(+)  MOG-35-55-specific pathogenic T-cell population and demonstrate successful treatment of EAE after disease onset. Suppression of disease was associated with reduced MOG-35-55-specific and non-specific T-cell production of interleukin-17a and interferon-γ in the central nervous system, as well as reduced numbers of CD4(+) and Foxp3(+) T cells in the central nervous system. With the use of Foxp3-GFP and Foxp3 conditional knockout mice, we demonstrate that the TCR CDR2 peptide treatment effect is dependent on the presence of Foxp3(+) regulatory T cells and that regulatory T cell numbers are significantly expanded in the periphery of treated mice. Hence, TCR CDR2 peptide therapy is effective in regulating heterogeneous, pathogenic T-cell populations through the activity of the Foxp3(+) regulatory T cell population.
Authors:
Abigail C Buenafe; Shayne Andrew; Halina Offner; Arthur A Vandenbark
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Immunology     Volume:  135     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-12     Completed Date:  2012-03-30     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  168-79     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / drug therapy,  immunology*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Antigen, T-Cell, alpha-beta / immunology*,  therapeutic use
T-Lymphocytes, Regulatory / immunology*
Grant Support
ID/Acronym/Agency:
NS23221/NS/NINDS NIH HHS; R01 NS023221/NS/NINDS NIH HHS; R01 NS023221-22/NS/NINDS NIH HHS; R01 NS023221-23/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Antigen, T-Cell, alpha-beta
Comments/Corrections

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