AUTHOR=Becker Christian , Bopp Tobias , Jonuleit Helmut 

TITLE=Boosting regulatory T cell function by CD4 stimulation enters the clinic

JOURNAL=Frontiers in Immunology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2012.00164

DOI=10.3389/fimmu.2012.00164

ISSN=1664-3224

ABSTRACT=<p>Understanding tolerance mechanisms at the cellular and molecular level holds the promise to establish novel immune intervention therapies in patients with allergy or autoimmunity and to prevent transplant rejection. Administration of mAb against the CD4 molecule has been found to be exceptionally well suited for intentional tolerance induction in rodent and non-human primate models as well as in humanized mouse models. Recent evidence demonstrated that regulatory T cells (Treg) are directly activated by non-depleting CD4 ligands and suggests Treg activation as a central mechanism in anti-CD4-mediated tolerance induction. This review summarizes the current knowledge on the role of Treg in peripheral tolerance, addresses the putative mechanisms of Treg-mediated suppression and discusses the clinical potential of harnessing Treg suppressive activity through CD4 stimulation.</p>