Title |
Chronic Inflammation Increases the Sensitivity of Mouse Treg for TNFR2 Costimulation
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Published in |
Frontiers in immunology, November 2017
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DOI | 10.3389/fimmu.2017.01471 |
Pubmed ID | |
Authors |
Tobias Schmid, Lena Falter, Sabine Weber, Nils Müller, Konstantin Molitor, David Zeller, Dorothea Weber-Steffens, Thomas Hehlgans, Harald Wajant, Sven Mostböck, Daniela N. Männel |
Abstract |
TNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. In vitro, TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported in vitro expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of bone marrow-derived immature myeloid cells in culture and reduced their suppressor function. In vivo application of TNCscTNF80-induced mild myelopoiesis in naïve mice without affecting the immune cell composition. Already a single application expanded Treg cells and improved suppression of CD4 T cells in mice with chronic inflammation. By contrast, multiple applications of the TNFR2 agonist were required to expand Treg cells in naïve mice. Improved suppression of T cell proliferation depended on expression of TNFR2 by T cells in mice repeatedly treated with TNCscTNF80, without a major contribution of TNFR2 on myeloid cells. Thus, TNFR2 activation on T cells in naïve mice can lead to immune suppression in vivo. These findings support the important role of TNFR2 for Treg cells in immune regulation. |
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