Foxp3+ regulatory T cells are activated in spite of B7‐CD28 and CD40‐CD40L blockade. Issue 4 (22nd February 2013)

• Record Type: Journal Article
• Authors: Vogel, Isabel; Verbinnen, Bert; Maes, Wim; Boon, Louis; Van Gool, Stefaan W.; Ceuppens, Jan L.
• Is Part Of: European journal of immunology. Volume 43:Issue 4(2013:Apr.)
• Page Start: 1013
• Page End: 1023
• Publication Date: 2013-02-22
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242737
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Costimulatory signals are required for priming and activation of naive T cells, while it is less clear how they contribute to induction of regulatory T (Treg)‐cell activity. We previously reported that the blockade of the B7‐CD28 and CD40L‐CD40 interaction efficiently suppresses allogeneic T‐cell activation in vivo. This was characterized by an initial rise in Foxp3<sup>+</sup> cells, followed by depletion of host‐reactive T cells. To further investigate effects of costimulatory blockade on Treg cells, we used an in vitro model of allogeneic CD4<sup>+</sup> cell activation. When CTLA‐4Ig and anti‐CD40L mAb (MR1) were added to the cultures, T‐cell proliferation and IL‐2 production were strongly reduced. However, Foxp3<sup>+</sup> cells proliferated and acquired suppressive activity. They suppressed activation of syngeneic CD4<sup>+</sup> cells much more efficiently than did freshly isolated Treg cells. CD4<sup>+</sup> cells activated by allogeneic cells in the presence of MR1 and CTLA‐4Ig were hyporesponsive on restimulation, but their response was restored to that of naive CD4<sup>+</sup> cells when Foxp3<sup>+</sup> Treg cells were removed. We conclude that natural Treg cells are less dependent on B7‐CD28 or CD40‐CD40L costimulation compared with Foxp3<sup>−</sup> T cells. Reduced costimulation therefore alters the balance between Teff and Treg‐cell activation in favor of Treg‐cell activity.</p> </abstract>