Skip Navigation



International Immunology Advance Access published online on February 13, 2008
International Immunology, doi:10.1093/intimm/dxn007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
20/4/471    most recent
dxn007v1
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
Google Scholar
Right arrow Articles by Razmara, M.
Right arrow Articles by Tykocinski, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Razmara, M.
Right arrow Articles by Tykocinski, M. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

CTLA-4·Ig converts naive CD4+CD25– T cells into CD4+CD25+ regulatory T cells

Marjaneh Razmara, Brendan Hilliard, Azadeh K. Ziarani, Youhai H. Chen and Mark L. Tykocinski

Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA

Correspondence to: Correspondence to: M. L. Tykocinski; E-mail: mlt4{at}mail.med.upen.edu

CTLA-4·Ig was originally designed as an immunosuppressive agent capable of interfering with the co-stimulation of T cells. In the present study, we demonstrate that CTLA-4·Ig, in combination with TCR ligation, has the additional capacity to convert naive CD4+CD25– T cells into Foxp3+ regulatory T (Treg) cells, as well as to expand their numbers. The CD4+CD25+Foxp3+ Treg generated by CTLA-4·Ig treatment in vitro potently suppress effector T cells. Extending this in vivo, we show that systemic administration of CTLA-4·Ig increases the percentage of CD4+CD25hiFoxp3+ cells within mixed lymphocyte reaction-induced murine lymph nodes. Significantly, the in vitro conversion of naive CD4+CD25– T cells into Treg cells is antigen-presenting cell (APC) dependent. This finding, together with the further observation that this conversion can also be driven in vitro by an antibody that engages B7-2 ligand, suggests that CTLA-4·Ig-driven Treg induction may be predicated upon active CTLA-4·Ig to B7-2 signaling within APC, which elicits from them Treg-inducing potential. These findings extend CTLA-4·Ig's functional repertoire, and at the same time, reinforce the concept that T cell anergy and active suppression are not entirely distinct processes and may be linked by some common molecular triggers.

Keywords: co-stimulation, CTLA-4·Ig, regulatory T cells

Transmitting editor: W. Strober

Received 31 August 2007, accepted 7 January 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




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.