Authors:	Schlöder, Janine Berges, Carsten Tüttenberg, Andrea Jonuleit, Helmut
Title:	Novel concept of CD4-mediated activation of regulatory T cells for the treatment of graft-versus-host disease
Online publication date:	21-Oct-2022
Year of first publication:	2017
Language:	english
Abstract:	Allogeneic hematopoietic stem cell transplantation (aHSCT) is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host-disease (GvHD) after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg), essential for the maintenance of peripheral immunologic tolerance, are in the focus of investigation. However, due to the limited number of tTreg in the peripheral blood, a complex, time and cost intensive in vitro expansion protocol is necessary for the production of an efficient cellular therapeutic. We demonstrated that activation of tTreg using the CD4-binding HIV-1 protein gp120 leads to a substantially increased suppressor activity of tTreg without the need for additional expansion. Gp120-activated tTreg prevent GvHD development in a preclinical humanized mouse model. In addition, gp120 is not only effective in prevention but also in therapy of GvHD by suppressing all clinical symptoms and improving survival of treated mice. These data indicate that tTreg activation by gp120 is a feasible and potent strategy for significant functional improvement of tTreg as cellular therapeutic for GvHD treatment without the need of complicated, time intensive and expensive in vitro expansion of isolated tTreg.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8140
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Frontiers in immunology 8
Pages or article number:	Art. 1495
Publisher:	Frontiers Media
Publisher place:	Lausanne
Issue date:	2017
ISSN:	1664-3224
Publisher URL:	http://dx.doi.org/10.3389/fimmu.2017.01495
Publisher DOI:	10.3389/fimmu.2017.01495
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)