Selective Activation of Tumor Necrosis Factor Receptor II Induces Antiinflammatory Responses and Alleviates Experimental Arthritis

Objective. Treg cells modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor II (TNFRII) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Treg cells. The purpose of the present study was to investigate the therapeutic activity of a novel TNFRII agonist in experimental arthritis as well as the role of different Treg cell subsets. Methods. A novel mouse TNFRII-selective fusion protein (EHD2-sc-mTNF(R2)) was generated by genetic engineering. Mouse T cells were incubated together with interleukin-2 and/or EHD2-sc-mTNF(R2), and the effects on Treg cells were analyzed by flow cytometry. Mice with collagen-induced arthritis (CIA) were treated with EHD2-sc-mTNF(R2) or saline, and the therapeutic effects were monitored and characterized. Results. Selective activation of TNFRII was found to expand both CD4+ and CD8+ Treg cells. Moreover, TNFRII activation elevated the number of CD4+CD25+ and CD8+CD25+ Treg cells and increased the number of FoxP3-expressing cells in CD8+, but not CD4+, Treg cells, indicating different mechanisms of TNFRII-induced expansion of diverse T cell subsets with suppressive activity. In the CIA model, we demonstrated that administration of the TNFRII agonist EHD2-sc-mTNF(R2) led to the expansion of both CD4+ and CD8+ Treg cells invivo and induced anti-inflammatory responses that alleviated arthritis. Conclusion. Our findings support the use of TNFRII-selective therapeutics as an effective approach to the treatment of arthritic disease and possibly other inflammatory and autoimmune diseases

Where to for the radical right in the European parliament? the rise and fall of transnational political cooperation

Amidst all the academic and media discussion in recent years of the causes and consequences of the rise in support for Radical Right parties (RRPs) in Europe, a related, but equally significant development, has generated less debate; namely the rise and fall in the European Parliament in 2007 of the trans-national Radical Right political group, Identity, Tradition and Sovereignty (ITS). Drawing on interviews with and a qualitative survey of former ITS members, as well as EP archival evidence, the paper begins by discussing why the notion of trans-national cooperation for Radical-Right political parties has proved difficult, and thus far has been doomed to failure, before analyzing the internal and external dynamics behind the rise and fall of the ITS group. Finally, the paper focuses on current collaboration among Radical Right parties post the June 2009 European elections and on the chances of a new trans-national far-right group emerging in the current parliament. © 2010 Taylor & Francis