The roadmap of immune suppression
Our bodies fight against foreign substances including microorganisms via the immune system. Under normal situations, immune cells are taught to distinguish between foreign and self-antigens. Central to this immunological tolerance are a population of T lymphocytes, known as regulatory T cells (Tregs). Although many aspects of Treg cell biology have been extensively studied, it remains to be determined what molecular changes occur in the cells that are being suppressed. In this context, the EU-funded 'Deciphering the molecular basis of regulatory T cell suppression' (TREG SUPPRESSION) project set out to characterise the molecular events that take place in CD4 T cells and dendritic cells, which are essentially the Treg targets. Researchers had previously shown that the suppressive activity of Tregs can be passed on to naive T cells through cell contact, implicating transforming growth factor (TGF)-beta signalling. During the TREG SUPPRESSION project, they extended this work and elucidated the pathway components that are activated following suppression by Tregs. Results revealed that deletion of the downstream inhibitor of TGF-beta signalling Smad 7 could induce atherosclerosis in transgenic mice. These atherosclerotic lesions were reduced upon transfer of Tregs, clearly indicating that Treg function through TGF-beta signalling is crucial for controlling inflammation. Adaptive transfer of Tregs in a clinical setting will be explored next in patients suffering from inflammatory disorders. Additionally, the findings of the project have triggered research into the inhibition of Treg cell function as a means of amplifying anti-cancer immune responses.
Keywords
Immune suppression, immunological tolerance, regulatory T cells, TGF-beta signalling
