Schmid, Tobias and Falter, Lena and Weber, Sabine and Mueller, Nils and Molitor, Konstantin and Zeller, David and Weber-Steffens, Dorothea and Hehlgans, Thomas and Wajant, Harald and Mostboeck, Sven and Maennel, Daniela N. (2017) Chronic Inflammation Increases the Sensitivity of Mouse Treg for TNFR2 Costimulation. FRONTIERS IN IMMUNOLOGY, 8: 1471. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)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 naive 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 naive 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 naive mice can lead to immune suppression in vivo. These findings support the important role of TNFR2 for Treg cells in immune regulation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; SUPPRESSIVE ACTIVITY; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; DENDRITIC CELLS; RECEPTOR; EXPANSION; EXPRESSION; MICE; inflammation; immune regulation; costimulation; MDSC; TNFR2; regulatory T cell |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 22 Feb 2019 08:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1861 |
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