“This review paper describes a central role transcription factor Foxp3 plays in development and function of a crucial subset of T cells...”

This is a review paper in one of the "super-hot" areas of immunology, and our laboratory has recently made significant contributions to this field. This particular field is both of fundamental interest and is also important for clinically relevant studies.

This review paper describes a central role transcription factor Foxp3 plays in the development and function of a crucial subset of T cells—so-called regulatory T cells—controlling autoimmunity, anti-tumor immunity, and immunity to infections. A series of studies performed in the laboratory by Jason Fontenot established a role for Foxp3 as regulatory T cell lineage specification factor and provided definitive answers to several outstanding issues in the field.

Most importantly, these studies unequivocally demonstrated that lack of regulatory T cells results in an early onset, highly aggressive, and fatal autoimmune pathology affecting multiple organs.

This review paper describes a central role transcription factor Foxp3 plays in development and function of a crucial subset of T cells controlling autoimmunity, anti-tumor immunity, and immunity to infections.

Our interest in regulatory T cell biology can be traced to a journal club on "historic papers" in immunology organized by first-year graduate students in the department. A heated discussion in one of these journal clubs discussing early work of Sir Peter Medawar* on neonatal tolerance precipitated our thinking and interest in the problem of "dominant tolerance".

It also coincided with Marc Gavin joining the lab at that time as a postdoctoral fellow and Marc was very interested in starting a new project on regulatory T cells. Another major event was identification of transcription factor Foxp3 by Fred Ramsdell and colleagues at the Bothell, Washington-based firm Celltech, who greatly helped us to jump-start Foxp3-related research.

The main problem we encountered was the very intense competition the massive amount of publication in these areas which resulted in a flood of data of varying quality being published in a rush.