| First Author | Schmid T | Year | 2017 |
| Journal | Front Immunol | Volume | 8 |
| Pages | 1471 | PubMed ID | 29163535 |
| Mgi Jnum | J:255999 | Mgi Id | MGI:6114350 |
| Doi | 10.3389/fimmu.2017.01471 | Citation | Schmid T, et al. (2017) Chronic Inflammation Increases the Sensitivity of Mouse Treg for TNFR2 Costimulation. Front Immunol 8:1471 |
| abstractText | 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. |
