Regulatory T cells: how do they find their space in the immunological arena?

After more of a decade of controversy, the concept of suppressor T cells initially promoted by Gershon, has now become an established paradigm. Current knowledge withholds that populations of suppressor or regulatory T cells (Treg cells) constitute a pivotal mechanism of immunological tolerance. Diverse types of Treg cells, with distinct origins, disparate and multiple functions have been described. However, despite the recognized importance of Treg cells in regulating immune responses, our understanding of their significance, mechanism of action and interplay with other means of immunological tolerance is still in its infancy. Increased comprehension of how Treg cells exert their function holds the promise for therapeutic intervention by manipulating one of the most sophisticated features of immunity to either boost responses in cancer and microbial diseases or suppresses those unwanted in autoimmunity and transplantation. Here, I will discuss new findings and open questions related to CD25(+)Treg cells in an attempt to cover some of the most puzzling aspects in the functioning of these cells.