TY  - JOUR
A1  - Helling, Bianca
A1  - König, Martin
A1  - Dälken, Benjamin
A1  - Engling, Andre
A1  - Krömer, Wolfgang
A1  - Heim, Katharina
A1  - Wallmeier, Holger
A1  - Haas, Jürgen
A1  - Wildemann, Brigitte
A1  - Fritz, Brigitte
A1  - Jonuleit, Helmut
A1  - Kubach, Jan
A1  - Dingermann, Theodor
A1  - Radeke, Heinfried H.
A1  - Osterroth, Frank
A1  - Uherek, Christoph
A1  - Czeloth, Niklas
A1  - Schüttrumpf, Jörg
T1  - A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway
T2  - Immunology and Cell Biology
N2  - CD4+CD25+ regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of the CD4 molecule that is not recognized by other anti-CD4 mAbs. We found that, due to this special epitope binding, BT-061 induces a unique phosphorylation of T-cell receptor complex-associated signaling molecules. This is sufficient to activate the function of Tregs without activating effector T cells. Furthermore, BT-061 does not induce the release of pro-inflammatory cytokines. These results demonstrate that BT-061 stimulation via the CD4 receptor is able to induce T-cell receptor-independent activation of Tregs. Selective activation of Tregs via CD4 is a promising approach for the treatment of autoimmune diseases where insufficient Treg activity has been described. Clinical investigation of this new approach is currently ongoing.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39384
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-393846
SN  - 0818-9641
SN  - 1440-1711
N1  - This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
VL  - 93.2015
SP  - 396
EP  - 405
PB  - Nature Publishing Group
CY  - Basingstoke
ER  -