Copyright
©2014 Baishideng Publishing Group Inc. All rights reserved.
CD28/CTLA-4/B7 and CD40/CD40L costimulation and activation of regulatory T cells
Isabel T Vogel, Stefaan W Van Gool, Jan L Ceuppens, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, University Hospital Gasthuisberg, 3000 Leuven, Belgium
Stefaan W Van Gool, Laboratory of Pediatric Immunology, KU Leuven, University Hospital Gasthuisberg, 3000 Leuven, Belgium
Author contributions: All authors contributed to this manuscript.
Correspondence to: Jan L Ceuppens, MD, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. jan.ceuppens@uzleuven.be
Telephone: +32-16-346137 Fax: +32-16-346035
Received: March 27, 2014
Revised: May 12, 2014
Accepted: June 10, 2014
Published online: July 27, 2014
Processing time: 121 Days and 22.9 Hours
Revised: May 12, 2014
Accepted: June 10, 2014
Published online: July 27, 2014
Processing time: 121 Days and 22.9 Hours
Core Tip
Core tip: Costimulation blockade (e.g., CD28/B7 and CD40/CD40L blockade) has been successfully used experimentally to induce tolerance to allo- or auto-antigens. Several studies suggest that effector T cells (Teff) and regulatory T cells (Treg) have different requirements regarding costimulation. While blockade of the CD40L receptor does not affect Treg cells and targets Teff cells, the effect of blocking the CD28/cytotoxic T lymphocyte antigen (CTLA)-4/B7 interaction (with CTLA-4Ig) is more difficult to predict and depends on the type, the strength and the stage of an immune process. Importantly, manipulating these costimulatory signals can therefore shift the Treg/Teff cell balance towards dominant Treg cell activity.